- σ-bonded organotransition-metal ions. Part IV. Kinetics and mechanism of the acid-catalysed decomposition of the 4- pyridiomethylpentacyanocobaltate(III) ion
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Potassium 4-pyridylmethylpentacyanocobaltate(III) monohydrate, prepared by the reaction of cobaltous cyanide with 4-bromomethylpyridinium bromide, is stable to air in aqueous solution. In solutions of pH 9·2 and below the pyridine ring is protonated to form the 4-pyridiomethylpentacyanocobaltate(III) ion and in perchloric acid of ca. 4M a second proton is added, presumably to one of the cyanide ligands. The kinetics of decomposition of these species have been investigated. In > 1M-perchloric acid the rate of decomposition increases linearly with increasing acid concentration to a maximum in ≥ 7·5M-acid, owing to the unimolecular decomposition of the protonated 4-pyridiomethylpentacyanocobalate(III) ion to the 4-cyanomethylpyridinium ion. At lower acidities (pH 1-5) the kinetics are complicated by the slowly established equilibrium between the 4-pyridiomethylpentacyanocobaltate(III) ion and the 4-pyridiomethylaquotetracyanocobaltate(III) ion and by the further decomposition of the latter ion at a rate comparable with the initial rate of approach to equilibrium. The kinetics in this pH region can however be simplified by the addition of small quantities of HCN sufficient to suppress the formation of the aquotetracyano-complex so that only the acid-catalysed decomposition of the pentacyano-complex is observed.
- Johnson,Tobe,Wong, Lai-Yoong
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Read Online
- Robust and Scalable Approach to 1,3-Disubstituted Pyridylcyclobutanes
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An approach to all isomeric 3-pyridylcyclobutane-derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five-step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3-dibromo-2,2-dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3-pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead-like compound library via reductive amination.
- Demchuk, Oleksandr P.,Hryshchuk, Oleksandr V.,Vashchenko, Bohdan V.,Radchenko, Dmytro S.,Kovtunenko, Volodymyr O.,Komarov, Igor V.,Grygorenko, Oleksandr O.
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Read Online
- Palladium and Nickel Catalyzed Suzuki Cross-Coupling with Alkyl Fluorides
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Suzuki cross-coupling of benzylic and unactivated aliphatic fluorides with aryl- and alkenylboronic acids has been achieved via mechanistically distinct Pd and Ni catalyzed pathways that outperform competing protodeboronation, β-hydride elimination, and h
- Balaraman, Kaluvu,Wolf, Christian
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supporting information
p. 8994 - 8999
(2021/11/20)
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- Mechanistic study of carboxylic acid and phosphate ester cleavage by oximate metal complexes surpassing the limiting reactivity of highly basic free oximate anions
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Two tridentate and one tetradentate new ligands containing the terminal oxime group separated from secondary amino and pyridine groups as additional binding sites by two or three methylene groups have been prepared. Their acid-base properties, as well as the composition and stability of their complexes with Zn(ii) and Cd(ii) ions, were determined by potentiometric and spectrophotometric titrations. The X-ray structure of a Cd(ii) complex of a related tridentate oxime ligand previously studied in solution was determined. All oximate complexes show high reactivity in the cleavage of aryl acetates, paraoxon, parathion and 4-nitrophenyl diphenyl phosphate, with rate constants significantly surpassing the limiting rate constants observed for highly basic free oximate anions. The second-order rate constants for individual oximate complexes in solution are assigned to each ligand, metal cation and substrate. The results of the cleavage of 4-substituted phenyl acetates were analyzed in terms of Br?nsted correlations with the leaving group pKa, which demonstrated a change in the rate determining step from the nucleophilic attack to the leaving group departure upon an increase in the leaving group basicity. The zero slope of the Br?nsted correlation for the nucleophilic attack indicates transition state stabilization through electrophilic assistance by the metal ion. This interpretation is supported by metal selectivity in the relative efficiency of the cleavage of paraoxon and parathion. The existence of the alpha-effect in ester cleavage by coordinated oximates is confirmed by an analysis of the Br?nsted correlations with the nucleophile basicity for metal bound oximate and alkoxo or hydroxo nucleophiles. The very high reactivity of the oximate complexes of the new ligands is attributed to transition state stabilization and to the removal of the solvational imbalance of oximate anions that impedes the expected increase in the reactivity of highly basic free anions.
- Flores-Alamo, Marcos,Gómez-Tagle, Paola,Lugo-González, José Carlos,Yatsimirsky, Anatoly K.
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supporting information
p. 2452 - 2467
(2020/03/05)
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- IMMUNOPROTEASOME INHIBITORS
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Provided herein are compounds, such as a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0360
(2019/06/09)
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- Mechanistic Insight Facilitates Discovery of a Mild and Efficient Copper-Catalyzed Dehydration of Primary Amides to Nitriles Using Hydrosilanes
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Metal-catalyzed silylative dehydration of primary amides is an economical approach to the synthesis of nitriles. We report a copper-hydride(CuH)-catalyzed process that avoids a typically challenging 1,2-siloxane elimination step, thereby dramatically increasing the rate of the overall transformation relative to alternative metal-catalyzed systems. This new reaction proceeds at ambient temperature, tolerates a variety of metal-, acid-, or base-sensitive functional groups, and can be performed using a simple ligand, inexpensive siloxanes, and low catalyst loading.
- Liu, Richard Y.,Bae, Minwoo,Buchwald, Stephen L.
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supporting information
p. 1627 - 1631
(2018/02/17)
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- Tetrazolylhydrazides as selective fragment-like inhibitors of the JumonjiC-domain-containing histone demethylase KDM4A
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The JumonjiC-domain-containing histone demethylase 2A (JMJD2A, KDM4A) is a key player in the epigenetic regulation of gene expression. Previous publications have shown that both elevated and lowered enzyme levels are associated with certain types of cancer, and therefore the definite role of KDM4A in oncogenesis remains elusive. To identify a novel molecular starting point with favorable physicochemical properties for the investigation of the physiological role of KDM4A, we screened a number of molecules bearing an iron-chelating moiety by using two independent assays. In this way, we were able to identify 2-(1H-tetrazol-5-yl)acetohydrazide as a novel fragment-like lead structure with low relative molecular mass (Mr=142 Da), low complexity, and an IC50 value of 46.6 μm in a formaldehyde dehydrogenase (FDH)-coupled assay and 2.4 μm in an antibody-based assay. Despite its small size, relative selectivity against two other demethylases could be demonstrated for this compound. This is the first example of a tetrazole group as a warhead in JMJD demethylases. Anchor fragment: To develop non-promiscuous metalloenzyme inhibitors, a metal-complexing acetohydrazide group was integrated in a tetrazolyl fragment, which can be matured into a scaffold to promote further selectivity at the ligand backbone binding site of these emerging drug targets.
- Rüger, Nicole,Roatsch, Martin,Emmrich, Thomas,Franz, Henriette,Schüle, Roland,Jung, Manfred,Link, Andreas
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supporting information
p. 1875 - 1883
(2015/11/10)
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- Metal-free, one-pot oxidative conversion of aldehydes to primary thioamides in aqueous media
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One-pot tandem reactions of a variety of aldehydes with aqueous ammonia, molecular iodine, and O,O-diethyl dithiophosphoric acid readily afford the corresponding primary thioamides. This is an inexpensive, practical, and metal-free way of accessing various thioamides from aldehydes in aqueous media. The pure products are obtained simply by filtration followed by successive washing with aqueous sodium thiosulfate and water. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Yadav, Arvind K.,Srivastava, Vishnu P.,Yadav, Lal Dhar S.
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supporting information
p. 408 - 416
(2014/01/06)
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- Exploratory process development and kilogram-scale synthesis of a novel oxazolidinone antibacterial candidate
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A concise, environmentally benign, and cost-effective route was developed for the large-scale preparation of 1, a novel oxazolidinone antibacterial candidate. The key intermediate 2-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl) pyridine 7 was prepared with high purity by mild deamination of the regioisomeric mixture 21. The mixture was prepared from a nucleophilic SNAr reaction by selective C-N coupling of the secondary amine functionality of 4-(pyridin-2-yl)-1H-pyrazol-3-amine 14 with 1,2-difluoro-4-nitrobenzene 10 in optimized conditions with the primary amine group remaining intact. The gaseous nitrogen release rate and reaction mixture temperature of the deamination step can be well controlled by altering the feeding manner, thereby providing safety guarantees. The optimized synthetic strategy of 1 with an overall yield of 27.6%, including seven sequential transformations by only five solid-liquid isolations, significantly improved the product separation workup. The strategy bypassed time-consuming and laborious procedures for any intermediate involved as well as for the final API. This study presents a process enabling the rapid delivery of a multikilogram quantity of API with high purity.
- Yang, Tao,Chen, Jia-Xiang,Fu, Yiwei,Chen, Kaixiao,He, Jinyun,Ye, Weiwei,Sang, Zitai,Luo, Youfu
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p. 511 - 519
(2014/05/06)
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- A heterogeneous palladium catalyst hybridised with a titanium dioxide photocatalyst for direct C-C bond formation between an aromatic ring and acetonitrile
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A palladium catalyst hybridised with a titanium dioxide photocatalyst can promote cyanomethylation of an aromatic ring by using acetonitrile, where the photocatalyst activates acetonitrile to form a cyanomethyl radical before the C-C bond formation using the palladium catalyst.
- Yoshida, Hisao,Fujimura, Yuki,Yuzawa, Hayato,Kumagai, Jun,Yoshida, Tomoko
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supporting information
p. 3793 - 3795
(2013/05/22)
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- Palladium-catalyzed cyanomethylation of aryl halides through domino Suzuki coupling-isoxazole fragmentation
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A one-pot protocol for the cyanomethylation of aryl halides through a palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester was developed. Mechanistically, the reaction proceeds through (1) Suzuki coupling, (2) base-induced fragmentation, and (3) deformylation as shown by characterization of all postulated intermediates. Under optimized conditions (PdCl2dppf, KF, DMSO/H2O, 130 °C) a broad spectrum of aryl bromides could be converted into arylacetonitriles with up to 88% yield.
- Velcicky, Juraj,Soicke, Arne,Steiner, Roland,Schmalz, Hans-Guenther
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supporting information; experimental part
p. 6948 - 6951
(2011/06/19)
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- Mild and practical method for the α-arylation of nitriles with heteroaryl halides
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A mild and transition-metal-free method for theα-arylation of a liphatic nitriles with activated heteroaryl halides was developed using NaHMDS o r KHMDS as base at ambient temperature. The key to the success of this method is generation of the nitrile anion in the presence of the heteroaryl halide. The method is applicable to both primary and secondary carbonitriles and a wide range of heteroaryl halides. Selective monoarylation was observed with primary carbonitriles. The operational simplicity and the mild reaction conditions add to the value of this methodas a practical alternative to the preparation of α-heteroaryl carbonitriles.
- Klapars, Artis,Waldman, Jacob H.,Campos, Kevin R.,Jensen, Mark S.,McLaughlin, Mark,Chung, John Y. L.,Cvetovich, Raymond J.,Chen, Cheng-Yi
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p. 10186 - 10189
(2007/10/03)
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- An insight of the reactions of amines with trichloroisocyanuric acid
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The reaction between amines or α-aminoacids with trichloroisocyanuric acid is studied under various conditions: N,N-dichloroamines, nitriles and ketones can be obtained from primary amines, while free aminoacids undergo oxidative decarboxylation to the corresponding nitrile of one less carbon atom.
- De Luca, Lidia,Giacomelli, Giampaolo
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p. 2180 - 2184
(2007/10/03)
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- Facile cyanomethylation of bromopyridines by nucleophilic substitution with lithioacetonitrile
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Substituted bromopyridines undergo facile nucleophilic substitution with lithioacetonitrile under mild conditions to afford the corresponding cyanomethylated products.
- Skerlj,Bogucki,Bridger
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p. 1488 - 1490
(2007/10/03)
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- FLASH VACUUM PYROLYSIS OF PYRIDINE N-OXIDES
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Pyridine N-oxide was pyrolysed under flash vacuum pyrolysis conditions to afford pyridine, pyrrole, 2-pyridone, 2-cyanomethylpyridine, and bipyridyls.Phenylpyridine N-oxides gave cyanonaphthalenes and naphthalene other than the above mentioned products.Pyrolysis of 2,6-disubstituted pyridine N-oxides provided the products which were supposed to be derived from the intramolecular oxygen migration.
- Itoh, Takashi,Ohsawa, Akio,Itoh, Yoshikuni,Igeta, Hiroshi
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p. 783 - 786
(2007/10/02)
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- Photostimulated Reactions of 2-Bromopyridine and 2-Chloroquinoline with Nitrile-Stabilized Carbanions and Certain Other Nucleophiles
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Potassiophenylacetonitrile (2) reacts with 2-bromopyridine (1) and 2-chloroquinoline (4) via the SRN1 mechanism when the reactants are exposed to near-UV light in liquid NH3.Potassioacetonitrile (6) reacts similarly with 1 and 4 upon photostimulation; however, the photo-SRN1 reaction with 1 is accompanied by SNAr2 amination which becomes the major reaction in the dark or in the presence of di-tert-butyl nitroxide.Substrate 4 undergoes competing SNAr2 amination with amide ion to form 2-aminoquinoline (10) and SN(ANRORC) reactions with both amide ion and carban ion 6 to form 3-methylquinazoline (11) and 2-methyl-3-cyanoquinoline (12), respectively.Formation of 12 becomes the major pathway in reactions between 4 and 6 carried out in the dark. 4-Picolylpotassium (14) reacts with 1, 4, and 4-bromopyridinium chloride (16) under photostimulation to form the appropriate dihetarylmethanes, along with the corresponding amino heterocycles.Amination of 1, 4, and 16 predominates when these reactions are carried out in the dark.Ammonium thiophenoxide (20) undergoes a slow photo-SRN1 reaction with 1 but fails to produce the expected 2-quinolyl phenyl sulfide with 4 after 2 h of irradiation.Potassium salts of acetylene, phenylacetylene, and phthalimide do not react with 1 or 4 after 2 h of exposure to near-UV light.
- Moon, Marcus P.,Komin, Andrew P.,Wolfe, James F.,Morris, Gene F.
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p. 2392 - 2399
(2007/10/02)
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