- A Facile Oxidation of Tertiary Amines to Lactams by Using Sodium Chlorite: Process Improvement by Precise pH Adjustment with CO 2
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By using cheap and innocuous sodium chlorite, a series of tertiary amines have been oxidized to the corresponding lactams with good selectivity and high yield. In this method, neither transition-metal catalyst nor oxidant was used. In the oxidation step, the pH of the sodium chlorite was precisely adjusted to pH around 6 using CO2, such pH is a compromise between oxidative properties, chemical stability, and unwanted precipitation. In addition, buffer salts are not necessary, which allows this oxidation reaction to be performed under safe and environmentally benign conditions.
- Liu, Chaoyang,Sun, Haozhou,Qin, Cheng,Yang, Tiannuo,Zhang, Wenxian,Zhou, Yuan,Li, Yani,Jia, Zheng Robert,Chu, Changhu
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p. 993 - 997
(2022/05/17)
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- Exploring Homogeneous Conditions for Mild Buchwald-Hartwig Amination in Batch and Flow
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Cross-couplings are among the most frequently used reactions in complex molecule synthesis. However, the requirement of stoichiometric base can cause challenges. Harsh, insoluble inorganic bases can lead to poor tolerance of sensitive functional groups, scale-up issues, and difficult adaptation to continuous flow platforms. Herein, we describe the use of high throughput experimentation to identify a number of conditions that enable Buchwald-Hartwig reactions to be carried out using readily available ligands (e.g., XantPhos) with DBU as a soluble, functional-group-tolerant, homogeneous base. Application of this system to diverse aminations in batch and flow are demonstrated, as is the translation of this technique to performing continuous Mizoroki-Heck and Sonogashira coupling reactions.
- Kashani, Saeed K.,Jessiman, Jacob E.,Newman, Stephen G.
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supporting information
p. 1948 - 1954
(2020/03/13)
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- Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs
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(S)-Blebbistatin is a widely used research tool to study myosin II, an important regulator of many motility based diseases. Its potency is too low to be of clinical relevance, but identification of analogs with enhanced potency could deliver leads for tar
- Verhasselt, Sigrid,Roman, Bart I.,Bracke, Marc E.,Stevens, Christian V.
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- Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under electron ionization and in the condensed phase
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Rationale: Mass spectrometry is known as an excellent method to predict the behavior of organic compounds in solution. The behavior of organic compounds in the gas phase inside the ion source of a mass spectrometer allows their intrinsic properties to be defined, avoiding the influence of intermolecular interactions, counter ions and solvent effects. Methods: Arylpyrrolidin-2-ones were obtained by condensed-phase synthesis from the corresponding N-arylcyclopropanecarboxamides. Electron ionization (EI) with accurate mass measurements by high-resolution time-of-flight mass-spectrometry and quantum chemical calculations were used to understand the behavior of the molecular radical cations of N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones in the ion source of a mass spectrometer. The geometries of the molecules, transition states, and intermediates were fully optimized using DFT-PBE calculations. Results: Fragmentation schemes, ion structures, and possible mechanisms of primary isomerisation were proposed for isomeric N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones. Based on the fragmentation pattern of the N-arylcyclopropanecarboxamides, isomerisation of the original M+? ions into the M+? ions of the N-arylpyrrolidin-2-ones was shown to be only a minor process. In contrast, this cyclization proceeds easily in the condensed phase in the presence of Br?nsted acids. Conclusions: Based on the experimental data and quantum chemical calculations the principal mechanism of decomposition of the molecular ions of N-arylcyclopropanecarboxamides involves their direct fragmentation without any rearrangements. An alternative mechanism is responsible for the isomerisation of a small portion of the higher energy molecular ions into the corresponding N-arylpyrrolidin-2-one ions. Copyright
- Lebedev, A. T.,Mazur, D. M.,Kudelin, A. I.,Fedotov, A. N.,Gloriozov, I. P.,Ustynyuk, Yu. A.,Artaev, V. B.
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p. 2416 - 2422
(2016/10/22)
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- Cobalt-catalyzed intermolecular C(sp2)-O cross-coupling
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Cobalt(II)-catalyzed C(sp2)-O cross-coupling between aryl/heteroaryl alcohols and vinyl/aryl halides in the presence of CuI has been achieved under ligand-free conditions. In this reaction, copper plays a significant role in transmetalation rather than being directly involved in the C-O coupling. This unique Co/Cu-dual catalyst system provides an easy access to a library of aryl-vinyl, heteroaryl-styryl, aryl-aryl, and heteroaryl-heteroaryl ethers in the absence of any ligand or additive.
- Kundu, Debasish,Tripathy, Manisha,Maity, Pintu,Ranu, Brindaban C.
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supporting information
p. 8727 - 8732
(2015/06/08)
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- Ligand-free Ullmann-type C-heteroatom couplings under practical conditions
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A new practical ligand-free protocol for copper-catalyzed C-heteroatom cross-coupling reactions (Ullmann-type) is described. The use of dimethyl sulfoxide (DMSO) as the solvent overcomes the need to use organic auxiliary ligands; thus, DMSO is revealed as a nontoxic and superior solvent for Ullmann-type coupling reactions. This method allows the arylation of a wide range of amides, alcohols, and amines under practical conditions with bromobenzene and iodobenzene derivatives and will likely find direct application in current organic synthesis. The competitive reactivity among different functional groups is reported and rationalized, and the possibility to achieve selective arylation reactions is demonstrated. Copyright
- Gueell, Imma,Ribas, Xavi
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p. 3188 - 3195
(2014/06/09)
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- Para-nitroblebbistatin, the non-cytotoxic and photostable myosin II inhibitor
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Blebbistatin, the best characterized myosin II-inhibitor, is commonly used to study the biological roles of various myosin II isoforms. Despite its popularity, the use of blebbistatin is greatly hindered by its blue-light sensitivity, resulting in phototo
- Kepiro, Miklos,Varkuti, Boglarka H.,Vegner, Laszlo,Voeroes, Gergely,Hegyi, Gyoergy,Varga, Mate,Malnasi-Csizmadia, Andras
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supporting information
p. 8211 - 8215
(2014/08/18)
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- Synthesis of ω-aminodithioesters
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ω-Aminodithioester derivatives were obtained from thionolactams by reaction with an alkyl triflate followed by thiolysis with hydrogen sulfide. The presence of an electron-withdrawing group was required on the N1 position (p-nitrophenyl or benzoyl) to favor the ring opening of γ-, δ- and ε-thionolactams. In the case of β-thionolactam, activation was provided by a CF2 motif in C3 position. Georg Thieme Verlag Stuttgart.
- Lacroix, Simon,Rixhon, Vinciane,Marchand-Brynaert, Jacqueline
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p. 2327 - 2334
(2008/02/03)
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- Ring-expanding reaction of cyclopropyl amides with triphenylphosphine and carbon tetrahalide
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We succeeded in activating cyclopropyl amides (monoactivated cyclopropane) through the corresponding imidoyl halides prepared in situ in the presence of 2 equiv of PPh3 and 1 equiv of CX4, and the ring-expanding products (N-substituted pyrrolidin-2-ones) were obtained in good yields. The reaction mechanism was investigated on the basis of oxygen-18 tracer experiment.
- Yang, Yong-Hua,Shi, Min
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p. 8645 - 8648
(2007/10/03)
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- HETEROCYCLIC COMPOUNDS
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The invention concerns blood clotting. The invention particularly concerns certain heterocyclic compounds, methods for the production thereof, their use for treating and/or preventing diseases, and their use for producing medicaments for treating and/or preventing diseases.
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Page/Page column 31
(2010/02/09)
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- Kinetics and mechanism of formation and decomposition of substituted 1-phenylpyrrolidin-2-ones in basic medium
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A study of chemical behaviour of substituted 4-chloro-N-phenylbutanamides in aqueous solutions of sodium hydroxide showed that the substrate first undergoes ring closure to give substituted 1-phenylpyrrolidin-2-ones, which are subsequently hydrolysed to substitution derivatives of sodium 4-amino-N-phenylbutanoates. Kinetic measurements provided the values of dissociation constants pKa and cyclization rate constants kc in water at 25°C for 2-bromo-4-chloro-N-(4-nitrophenyl)butanamide [pKa = 11.64 ± 0.01; kc = (1.94 ± 0.03) × 10-2 s-1], 4-chloro-N-(4-nitrophenyl)butanamide [pKa = 13.35 ± 0.02; kc = (1.60 ± 0.02) × 10-2 s-1 and 4-chloro-2-methyl-N-(4-nitrophenyl)butanamide [pKa = 13.55 ± 0.03; kc = (7.61 ± 0.11) × 10-2 s-1]. The pKa and kc values of individual derivatives differ depending on the substitution at the α-position of the butanamide skeleton. In methanolic sodium methoxide solutions, the course of ring closure of 2-bromo-4-chloro-N-(4-nitrophenyl)butanamide is of similar nature but slower [K = 60.10 ± 0.08 and kc = (6.52 ± 0.05) × 10-3 s-1]. The subsequent hydrolyses of substituted 1-phenylpyrrolidin-2-ones to substituted 4-aminobutanoic acids also have different courses with different derivatives and depend on the substituents in the aromatic and/or heterocyclic moiety. The rate-limiting step of hydrolysis of 1-(4-nitrophenyl)pyrrolidin-2-one consists of the non-catalysed decomposition of the tetrahedral intermediate. In the case of 3-bromo-1-(4-nitrophenyl)pyrrolidin-2-one at sodium hydroxide concentrations below 0.1 mol 1-1, the rate-limiting step is the second reaction pathway, i.e. the hydroxide ion-catalysed decomposition of the tetrahedral intermediate. At sodium hydroxide concentrations above 0.1 mol 1-1], the rate-limiting step shifts to formation of the tetrahedral intermediate. This formation of the intermediate is 140 times slower than its hydroxide ion-catalysed decomposition [k3/k-1 = (1.40 ± 0.04) × 102 1 mol-1]. Introduction of a 3-bromo substituent into 1-(4-nitrophenyl)pyrrolidin-2-one results in acceleration of all the reaction steps of hydrolysis and increases the acidity of the intermediate. Copyright
- Sedlak, Milos,Hejtmankova, Ludmila,Kasparova, Pavla,Kavalek, Jaromir
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p. 165 - 173
(2007/10/03)
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- Kinetics and Equilibria of Ring Closure through an Amide Linkage. Part 2. 1-Aryl-2-pyrrolidones
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Equilibrium constants, and rate constants for forward and reverse reactions, for ring closure of several 4-(arylamino)butanoic acids to 1-aryl-2-pyrrolidones in aqueous acid, together with ionisation constants of the former group of compounds, are reported.The equilibrium constants K at 50 deg C between neutral protonic forms of open-chain and ring compounds are related to the ionisation constants of the nitrogen-protonated 4-(arylamino)butanoic acids, K1, by the equation: log K=0.70 (pK1)+1.53.The value of K for pyrrolidone itself was measured for comparison.Studies of 18O exchange reveal that (except in the case of the substrate which bears the most electron-withdrawing substituents in the aryl ring, namely 2,4-dinitro) the rate-determining step lies between the tetrahedral intermediate and the ring compound.Substituent effects and solvent deuterium isotope effects on the hydronium-ion catalysed reaction are consisitent with a transition state close to the neutral tetrahedral intermediate.The effects of methyl substituents in the heterocyclic ring on rate and equilibrium constants have also been studied.The variation of K with temperature, and derived thermodynamic parameters, are reported in two cases.
- Abdallah, Jassim M.,Moodie, Roy B.
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p. 1243 - 1250
(2007/10/02)
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