- Experimental and Computational Studies towards Chemoselective C?F over C?Cl Functionalisation: Reversible Oxidative Addition is the Key
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Catalytic cross-coupling is a valuable tool for forming new carbon-carbon and carbon-heteroatom bonds, allowing access to a variety of structurally diverse compounds. However, for this methodology to reach its full potential, precise control over all competing cross-coupling sites in poly-functionalised building blocks is required. Carbon-fluorine bonds are one of the most stable bonds in organic chemistry, with oxidative addition at C?F being much more difficult than at other C-halide bonds. As such, the development of methods to chemoselectively functionalise the C?F position in poly-halogenated arenes would be very challenging if selectivity was to be induced at the oxidative addition step. However, metal-halide complexes exhibit different trends in reactivity to the parent haloarenes, with metal-fluoride complexes known to be very reactive towards transmetalation. In this current work we sought to exploit the divergent reactivity of Ni?Cl and Ni?F intermediates to develop a chemoselective C?F functionalisation protocol, where selectivity is controlled by the transmetalation step. Our experimental studies highlight that such an approach is feasible, with a number of nickel catalysts shown to facilitate Hiyama cross-coupling of 1-fluoronapthalene under base free conditions, while no cross-coupling with 1-chloronapthalene occurred. Computational and experimental studies revealed the importance of reversible C?Cl oxidative addition for the development of selective C?F functionalisation, with ligand effects on the potential for reversibility also presented.
- Jacobs, Emily,Keaveney, Sinead T.
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p. 637 - 645
(2020/12/07)
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- 3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL)PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS
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A compound of formula (I) or a salt thereof are provided wherein R1, X and R3 are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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Page/Page column 41; 49
(2015/07/07)
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- Ligand-free, palladium-catalyzed dihydrogen generation from TMDS: Dehalogenation of aryl halides on water
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A mild and environmentally attractive dehalogenation of functionalized aryl halides has been developed using nanoparticles formed from PdCl2 in the presence of tetramethyldisiloxane (TMDS) on water. The active catalyst and reaction medium can be recycled. This method can also be applied to cascade reactions in a one-pot sequence.
- Bhattacharjya, Anish,Klumphu, Piyatida,Lipshutz, Bruce H.
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supporting information
p. 1122 - 1125
(2015/03/14)
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- Triton B-mediated efficient and convenient alkoxylation of activated aryl and heteroaryl halides
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A simple and convenient one-pot synthesis of aryl alkyl ethers by the alkoxylation of aryl halides with alcohol in the presence of Triton B as a base is described. The procedure is applicable for a variety of aryl and heteroaryl halides, and yields are very good. The use of a nonmetallic base and solvent-free conditions are important features of the reaction. Copyright Taylor & Francis Group, LLC.
- Meshram,Goud, P. Ramesh,Reddy, B. Chennakesava,Kumar, D. Aravind
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experimental part
p. 2122 - 2129
(2010/08/13)
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- KINASE INHIBITORS AND METHODS OF USE
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The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.
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Page/Page column 83-84
(2010/04/03)
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- Catalytic process for regiospecific chlorination of alkanes, alkenes and arenes
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The present invention provides a process for regiospecific chlorination of an aromatic or aliphatic compound with a chlorine source comprising a metal chloride and other than Cl2and SO2Cl2in presence of hypervalent iodine catalyst and in acidic medium.
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Page column 6
(2008/06/13)
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- NaIO4-Mediated Selective Oxidative Halogenation of Alkenes and Aromatics Using Alkali Metal Halides
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(Equation presented) NaIO4 oxidizes alkali metal halides efficiently in aqueous medium to halogenate alkenes and aromatics and produce the corresponding halo derivatives in excellent regio and stereoselectivity. The system also demonstrates the asymmetric version of bromo hydroxylation using β-cyclodextrin complexes, resulting in moderate ee.
- Dewkar, Gajanan K.,Narina, Srinivasarao V.,Sudalai, Arumugam
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p. 4501 - 4504
(2007/10/03)
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- Kinetic studies of the reactions of some phenols and alkyl aryl ethers with dinitrogen pentoxide in perfluorocarbon solvents
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The reaction of dinitrogen pentoxide in perfluorocarbon solvents with phenols and alkyl aryl ethers carrying halogeno ring-substituents results in nitrodehydrogenation. Rate measurements show that the preferred orientation of nitration is ortho > para > meta to the hydroxy group; the kinetic isotope effect, kH/kD, has a value close to unity. Phenols show considerably higher reactivity than similarly substituted alkyl phenyl ethers, and a mechanism is suggested involving initial interaction of N2O5 with the hydroxy function followed by reaction via cyclic transition states.
- Crampton,Gibbons,Millar
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p. 1662 - 1665
(2007/10/03)
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- Chemoselective O-methylation of phenols under non-aqueous condition
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Chemoselective O-methylation of substituted phenols takes place in dry. tetrahydrofuran (THF) in the presence of LiOH.H2O and dimethylsulfate (DMS). Quantitative methyl transfer from DMS preserves the atom economy.
- Basak, Anindita,Nayak, Mrinal K.,Chakraborti, Asit K.
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p. 4883 - 4886
(2007/10/03)
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- Photochemical Nitration by Tetranitromethane. X. A Possible Addition/Elimination Pathway to Trinitromethylaromatic Compounds
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The photolysis of tetranitromethane and 4-chloroanisole in dichloromethane at +20, -20 and -50 deg C led to the formation of mainly 4-chloro-2-trinitromethylanisole (40-50percent yield) and a pair of adducts (ca. 30percent yield) in which nitrito/trinitromethyl addition had taken place across the 2,5-positions of 4-chloroanisole.Small amounts of a pair of labile adducts (2-3percent yield), assigned the structure of the analogous hydroxy/trinitromethyl adducts were formed in the beginning of the runs.In acetonitrile, the major product from the same reaction was 4-chloro-2-nitroanisole at all three temperatures.Only at -50 deg C were the nitrito/trinitromethyl adducts detectable in low yield (1-2percent).The pair of nitrito/trinitromethyl adducts spontaneously decomposed in acetonitrile to give 4-chloro-2-trinitromethylanisole with rate constants of 7*10-4 min-1 at 0 deg C and 0.020 min-1 at 20 deg C, implying that they should be stable in this solvent at -20 and -50 deg C, if formed.The adducts also decomposed to 4-chloro-2-trinitromethylanisole under photochemical conditions accounting for the formation of this compound in low yield also in acetonitrile.The nitration process predominantly observed in acetonitrile presumably occurs via coupling of 4-chloroanisole radical cation and NO2, both formed in the initial photochemical step.The nitrito/trinitromethyl adducts were thermally and photochemically stable in dichloromethane under the reaction periods employed for photolysis.The conversion into labile hydroxy/trinitromethyl adducts was assumed to occur via acid-catalysed hydrolysis, eventually leading to 4-chloro-2-trinitromethylanisole via acid-promoted elimination of water from the latter adducts.However, only a minor part of this compound can be accounted for in this way.
- Eberson, Lennart,Hartshorn, Michael P.,Svensson, Jan Olof
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p. 925 - 934
(2007/10/02)
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- 13C NMR Spectra of Substituted o-Nitroanisoles and n-Butyl o-Nitrophenyl Ethers
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13C NMR analyses of substituted o-nitroanisoles and n-butyl o-nitrophenyl ethers are reported. Key Words: 13C NMR - o-Nitroanisoles - n-Butyl o-nitrophenyl ethers
- Zeegers, Petrus J.,Thompson, Malcolm J.
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p. 497 - 499
(2007/10/02)
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- ipso Nitration in p-halophenyl ethers
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Addition of nitronium ion ipso to halogen occurs on nitration of the p-haloanisoles in acetic anhydride at -60 deg C.In the cases of p-fluoro- and p-chloro-anisole, addition of the nitronium ion is reversible and only small amounts of ipso products are obtained.With p-bromoanisole nitrodebromination occurs.When p-halophenyl ethers containing a trapping substituent, e.g., 2-(4-chlorophenoxy)-2-methylpropanoic acid, are used as substrates, substantial amounts of the spiro diene with nitro ipso to halogen, e.g., 3,3-dimethyl-8-chloro-8-nitro-1,4-dioxaspirodeca-6,9-dien-2-one, can be isolated.The results demonstrate that extensive ipso attack at the halogen-substituted position is general in the nitration of p-halophenyl ethers.Key words: ipso nitration, ether, diene, p-haloanisole.
- Clewley, Robin G.,Fischer, Alfred,Henderson, George N.
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p. 1472 - 1479
(2007/10/02)
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- Electrophilic Aromatic Substitution. Part 28. The Mechanism of Nitration of Some 4-Substituted Anisoles and Phenols, and of Rearrangement of the Intermediate 4-Nitro-4-substituted-cyclohexa-2,5-dienones
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The kinetics of nitration in sulphuric acid of 2-chloro-4-methyl-, 4-chloro-, 2,4-dichloro-, and 4-fluoroanisole and of the corresponding phenols have been determined.The reaction products from the anisoles and from 2-chloro-4-methyl- and 4-fluoro-phenol have been determined.Results for 4-methylanisole supplementary to earlier ones are also reported.Generally the anisoles give the 2-nitro-derivatives and the 2-nitrophenols, and from 2-chloro-4-methylanisole, 2-chloro-4-methyl-4-nitrocyclohexa-2,5-dienone was formed as an intermediate.The decomposition of this dienone in sulphuric acid, like those of others, changes from a non-acid-catalysed to an acid-catalysed form with increasing acidity.The first form is regarded as a decomposition into an aryloxyl radical and nitrogen dioxide which can recombine to give the 2-nitrophenol.The formation of a small amount of 2-(4-fluorophenoxy)-4-fluorophenol in the nitration of 4-fluorophenol is seen as support for this view.The acid-catalysed form is regarded as the decomposition of the protonated dienone into a phenol-nitronium ion encounter-pair which can give the nitrophenol.A consequence of the mechanism is that if the phenol were nitrated at less than the encounter rate, the phenol itself would in appropriate conditions be a product of the ipso-nitration of the original anisole. 4-Methyl-, 2-chloro-4-methyl-, and 4-chloro-phenol have been so identified.Quantitative analysis of the results allows evaluation of the partitioning of dienone decomposition between the two modes.The mechanism accounts for the formation from 2,4-dichloro-anisole of both 2,4-dichloro-6- and 2,4-dichloro-5-nitroanisole, but only 2,4-dichloro-6-nitrophenol.
- Bloomfield, Colin,Manglik, Ajay K.,Moodie, Roy B.,Schofield, Kenneth,Tobin, Geoffrey D.
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- N-Substituted 2-methoxybenzenesulphonamides and medicaments containing them
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The invention relates to new N-substituted benzenesulphonamides of general formula STR1 in which N IS 2 OR 3, R1 and R2 are hydrogen atoms, methyl, ethyl groups, or jointly form with the nitrogen a nitrogenized heterocyclic ring having 5 or 6 members, in particular a piperidino, pyrrolidino or morpholino group, R3 is a hydrogen atom, an NO2 group, an NH2 group, or a halogen, R4 is a hydrogen, a halogen, an NH2 group or a sulphonamide group. These compounds are useful as active substances of medicaments, in particular as antiemetic.
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