- Quantifying Through-Space Substituent Effects
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The description of substituents as electron donating or withdrawing leads to a perceived dominance of through-bond influences. The situation is compounded by the challenge of separating through-bond and through-space contributions. Here, we probe the experimental significance of through-space substituent effects in molecular interactions and reaction kinetics. Conformational equilibrium constants were transposed onto the Hammett substituent constant scale revealing dominant through-space substituent effects that cannot be described in classic terms. For example, NO2 groups positioned over a biaryl bond exhibited similar influences as resonant electron donors. Meanwhile, the electro-enhancing influence of OMe/OH groups could be switched off or inverted by conformational twisting. 267 conformational equilibrium constants measured across eleven solvents were found to be better predictors of reaction kinetics than calculated electrostatic potentials, suggesting utility in other contexts and for benchmarking theoretical solvation models.
- Adam, Catherine,Burns, Rebecca J.,Cockroft, Scott L.,Mati, Ioulia K.,Muchowska, Kamila B.
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supporting information
p. 16717 - 16724
(2020/07/24)
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- Palladium dichloride adduct of N,N-bis-(diphenylphosphanylmethyl)-2- aminopyridine: Synthesis, structure and catalytic performance in the decarboxylative cross-coupling of 4-picolinic acid with aryl bromide
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Reaction of PdCl2 with N,N-bis-(diphenylphosphanylmethyl)-2- aminopyridine (bdppmapy) afforded a mononuclear complex [(bdppmapy)PdCl 2] (1). Compound 1 was characterized by elemental analysis, IR, 1H, 13C and 31P NMR, electrospray ion mass spectra (ESI-MS) and X-ray single crystal crystallography. The Pd(ii) center in 1 is chelated by bdppmapy, showing a cis-square planar geometry. With the assistance of additive Cu2O, complex 1 exhibited good catalytic activity toward the decarboxylative cross-coupling reactions between 4-picolinic acid and aryl bromides. In the presence of only 2 mol% catalyst, a family of 4-aryl-pyridines could be isolated in up to 83% yield.
- He, Run-Tian,Wang, Jian-Feng,Wang, Hui-Fang,Ren, Zhi-Gang,Lang, Jian-Ping
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p. 9786 - 9794
(2014/06/23)
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- Metal-free arylation of benzene and pyridine promoted by amino-linked nitrogen heterocyclic carbenes
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An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown to mediate carbon-carbon coupling through the direct C-H functionalization of benzene and pyridine in the absence of a metal catalyst. Using EPR, the first spectroscopic evidence corroborating the single electron transfer mechanism for the metal-free carbon-carbon coupling manifold, as reported by others, is introduced.
- Chen, Wen-Ching,Hsu, Yu-Chen,Shih, Wei-Chun,Lee, Ching-Yu,Chuang, Wen-Han,Tsai, Yi-Fang,Chen, Peter Ping-Yu,Ong, Tiow-Gan
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supporting information; experimental part
p. 6702 - 6704
(2012/07/14)
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- Selenium dioxide-mediated methoxyhydroxylation of cyclic arylolefin
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Selenium dioxide-mediated methoxyhydroxylation of cyclic arylolefin with the modest yields is described. This facile strategy was also used to synthesize several 4-arylpyridines, 3-hydroxy-4-arylpyridines, and 3,4-diarylpyridines. Crown Copyright
- Chang, Meng-Yang,Lin, Chung-Han,Chen, Yeh-Long
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scheme or table
p. 1430 - 1433
(2010/05/03)
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- AZABENZIMIDAZOLYL COMPOUNDS
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I), as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Page/Page column 66
(2008/06/13)
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- BENZIMIDAZOLYL COMPOUNDS AS POTENTIATORS OF MGLUR2 SUBTYPE OF GLUTAMATE RECEPTOR
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Page/Page column 70
(2010/11/30)
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- Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations
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This article describes the design, optimisation and development of a Suzuki cross-coupling protocol mediated by an efficient palladium-en-capsulated catalyst (Pd EnCat) under microwave irradiation. The methodology has been used in both batch mode for classical library preparation and in continuous-flow applications furnishing multigram quantities of material. Described is a method that uses direct focused microwave heating whilst applying an external cooling source. This enables a lower than normal bulk temperature to be maintained throughout the reaction period leading to significant improvements in the overall yield and purity of the reaction products. Additional aspects of this novel heating protocol are discussed in relation to the prolonged lifetime and enhanced reactivity of the immobilised catalyst system.
- Baxendale, Ian R.,Griffiths-Jones, Charlotte M.,Ley, Steven V.,Tranmer, Geoffrey K.
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p. 4407 - 4416
(2008/02/07)
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- Radical dearomatization of arenes and heteroarenes
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The stannane-mediated benzeneselenol-catalyzed addition of aryl iodides to a range of arenes and aromatic hetereocycles has been studied. With furan, thiophene, and several carbocyclic arenes, the addition takes place with quenching of the adduct radical by the catalytic selenol leading to moderate yields of aryl-dihydroarenes. With nitrogen heterocycles, on the other hand, it was not possible to suppress aromatization of the adduct radical and fully aromatized products were isolated. Aryl iodides bearing hydrogen bond donating groups in the ortho-position add to nitrogen heterocycles with high selectivity ortho- to the nitrogen, affording a simple one-step synthesis of potential chelating ligands. While 2-iodophenol is an excellent aryl radical source in these reactions, the homologous 1-iodo-2-naphthol fails owing to its reaction with diphenyl diselenide, which gives 1-phenylseleno-2-naphthol in high yield.
- Crich, David,Patel, Mitesh
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p. 7824 - 7837
(2007/10/03)
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- Pyridino-directed lithiation of anisylpyridines: New access to functional pyridylphenols
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The lithiation of nine anisylpyridines has been studied. While usual reagents did not react or gave addition products on pyridine ring, the BuLi-LiDMAE (LiDMAE=Me2N(CH2)2OLi) superbase induced exclusive pyridino directed metallation. The usefulness of this new reaction allowed the efficient preparation of a range of alpha functional pyridylphenols. A successful subsequent cyclisation of an appropriate isomer into corresponding benzofuropyridine was also performed.
- Parmentier, Micha?l,Gros, Philippe,Fort, Yves
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p. 3261 - 3269
(2007/10/03)
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- Direct synthesis of heterobiaryls by radical addition to pyridine: Expeditious synthesis of chelating ligands
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The addition of aryl radicals to pyridine may be affected in moderate yield on exposure of aryl iodides to tributyltin hydride, AIBN, and diphenyl diselenide in hot pyridine. Mixtures of ortho-, meta-, and para-aryl substituted pyridines are typically obtained. When the iodide is ortho-substituted with a hydrogen bond donor, such as o-iodophenol, significantly improved selectivity for ortho-substituted pyridines, with potential as bidentate chelating ligands, is obtained.
- Crich, David,Patel, Mitesh
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p. 499 - 504
(2007/10/03)
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- Synthesis and deprotonation of 2-(pyridyl)phenols and 2-(pyridyl)anilines
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2-(2- and 3-Pyridyl)anilines (1, 2), 2,2-dimethyl-N-[2-(2- and 3-pyridyl)phenyl]propanamides (3, 4), and 2-, 3- and 4-(2-methoxyphenyl)pyridines (7-9) are readily synthesized using cross-coupling reactions. Whereas the amines 1, 2 undergo side reactions, the corresponding amides 3, 4 are deprotonated with lithium 2,2,6,6-tetramethylpiperidide (LTMP): the compound 3 at C6′ under in situ quenching, and the compound 4 at C4′. When the ether 7 is subjected to the same reagent, lithiation occurs at C6′.
- Rebstock, Anne-Sophie,Mongin, Florence,Trecourt, Francois,Queguiner, Guy
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p. 3064 - 3068
(2007/10/03)
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- Model reactions for the synthesis of azacorannulenes and related heteroaromatic compounds
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4-(2-Ethynylphenyl)pyridine (10), 3-(2-ethynylphenyl)pyridine (11), 2-(2-trimethylsilylethynylphenyl)pyridine (26), and 3-ethynyl-2-phenylpyridine (13) were prepared from readily available pyridine precursors by standard coupling reactions. Pyrolysis of 10 at 810 °C/0.5 Torr provided benzo[f]isoquinoline (45) and the benzopentalene dimer 47. Pyrolysis of 11 (820 °C/0.5 Torr) afforded benzo[f]quinoline (50), benzo[h]i-soquinoline (52), and a mixture of isomers of 47. Pyrolysis of 13 (820 °C/0.3 Torr) provided benzo[h]quinoline (56) and the novel azulene derivative azuleno[1,2-b]pyridine (58). When 26 was desilylated by treatment with TBAF in THF/water, the unusual "dimerization" product 37 was produced; its structure was confirmed by X-ray structural analysis. The mechanisms of these transformations are discussed. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Dix, Ina,Doll, Christian,Hopf, Henning,Jones, Peter G.
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p. 2547 - 2556
(2007/10/03)
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- α1-Adrenoceptor agonists: The identification of novel α1A subtype selective 2′-heteroaryl-2-(phenoxymethyl)imidazolines
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Novel 2′-heteroaryl-2-(phenoxymethyl)imidazolines have been identified as potent agonists of the cloned human α1-adrenoceptors in vitro. The nature of the 2′-heteroaryl group can have significant effects on the potency, efficacy, and subtype selectivity in this series. α1A Subtype selective agonists have been identified.
- Bishop, Michael J.,Barvian, Kevin A.,Berman, Judd,Bigham, Eric C.,Garrison, Deanna T.,Gobel, Michael J.,Hodson, Stephen J.,Irving, Paul E.,Liacos, James A.,Navas, Iii, Frank,Saussy Jr., David L.,Speake, Jason D.
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p. 471 - 475
(2007/10/03)
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- Synthesis of functionalized 4-phenyl-pyridines via electrochemically prepared organozinc reagents
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The efficient and convenient synthesis of various functionalized 4-phenyl-pyridines 2 is described. The key step of the procedure is the electrochemical formation of aromatic organozinc reagents 1 and their coupling with pyridinium salts. Intermediate 1,4
- Gall, Erwan Le,Gosmini, Corinne,Nédélec, Jean-Yves,Périchon, Jacques
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p. 1923 - 1927
(2007/10/03)
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- Potassium peroxodisulfate: A convenient oxidizing agent for aromatization of 1,4-dihydropyridines
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A series of 13 different 4-substituted 2,6-dimethyl-3,5-diethoxycarbonyl)-1,4-dihydropyridines have been oxidized to pyridine derivatives by potassium peroxodisulfate in dry and wet acetonitrile solution at reflux condition. Formation of two kinds of products has been observed depending on the type of 4-substituent. Addition of water affects only the rate of oxidation.
- Memarian,Mohammadpoor-Baltork,Sadeghi,Samani
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p. 727 - 728
(2007/10/03)
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- The palladium catalysed Suzuki coupling of 2- and 4-chloropyridines
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The Suzuki coupling of 2- and 4-chloropyridines with arylboronic acids is successfully performed under Pd(PPh3)4 catalysis. Moderate to good yields are obtained with 4-chloropyridines while 2-chloropyridines give excellent yields. The corresponding pyridine N-oxides react in the same manner. An easy and cheap access to arylpyridines, a class of compound with medicinal interest, is thus achieved.
- Lohse, Olivier,Thevenin, Philippe,Waldvogel, Erwin
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- A NEW APPROACH FOR PREPARATION OF ATROPISOMERS OF ARYLPYRIDYLS VIA CROSS-COUPLING REACTIONS OF ARYL 2-(3-SUBSTITUTED)PYRIDYL SULFOXIDES WITH GRIGNARD AND ORGANOLITHIUM REAGENTS
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The cross-coupling reactions of phenyl 2-(3-substituted)pyridyl sulfoxides with 2-methoxyphenyl- and 1-(2-methoxy)naphthyl Grignard and 2-phenoxyphenyl lithium reagents afforded atropisomers of arylpyridyl derivatives in good yields which undergo thermal epimerization.
- Shibutani, Tadao,Fujihara, Hisashi,Furukawa, Naomichi
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p. 2943 - 2946
(2007/10/02)
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- THE PYRIDYL CATION AS A REACTIVE INTERMEDIATE IN THE PHOTOREACTION OF IODOPYRIDINES WITH BENZENES
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The electrophilic behavior of the reactive entity in the photosubstitution of benzenes with 2-iodopyridine was found to be ascribable to the intermediary 2-pyridyl cation, rather than the electrophilic 2-pyridyl radical.
- Ohkura, Kazue,Seki, Koh-ichi,Terashima, Masanao,Kanaoka, Yuichi
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p. 3433 - 3436
(2007/10/02)
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- REGIOSELECTIVE SYNTHESIS OF 2-SUBSTITUTED PYRIDINES VIA GRIGNARD ADDITION TO 1-(ALKOXYCARBOXY)-PYRIDINIUM SALTS
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A regioselective one pot synthesis of 2-substituted pyridine derivatives from pyridine-1-oxides is described.
- Webb, Thomas R.
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p. 3191 - 3194
(2007/10/02)
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- Hydroxyphenyl-1-methylpyridinium-iodide as Potential Reactivators of Acetylcholinesterase Poisoned with Organophosphorus Compounds
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It was our aim to reactivate acetylcholinesterase poisoned with sarin.We synthesized 2-(o-hydroxyphenyl)-1-methylpyridinium-iodide (9), 2-(p-hydroxyphenyl)-1-methylpyridinium-iodide (19) and 4-(o-hydroxyphenyl)-1-methylpyridinium-iodide (14) as potential reactivators.All substances showed moderate toxicity against mice; their reactivity potency in vitro and in vivo was negligible.
- Riggio, Gaetano,Hopff, Wolfgang Herbert,Hofmann, Alfred Andre,Waser, Peter Gaudenz
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p. 1039 - 1045
(2007/10/02)
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