108-47-4Relevant articles and documents
Flow synthesis of 2-methylpyridines via α-methylation
Manansala, Camille,Tranmer, Geoffrey K.
, p. 15797 - 15806 (2015)
A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch reaction protocols. Eight 2-methylated pyridines were produced by progressing starting material through a column packed with Raney nickel using a low boiling point alcohol (1-propanol) at high temperature. Simple collection and removal of the solvent gave products in very good yields that were suitable for further use without additional work-up or purification. Overall, this continuous flow method represents a synthetically useful protocol that is superior to batch processes in terms of shorter reaction times, increased safety, avoidance of work-up procedures, and reduced waste. A brief discussion of the possible mechanism(s) of the reaction is also presented which involves heterogeneous catalysis and/or a Ladenberg rearrangement, with the proposed methyl source as C1 of the primary alcohol.
Bimetallic C-C Bond-Forming Reductive Elimination from Nickel
Xu, Hongwei,Diccianni, Justin B.,Katigbak, Joseph,Hu, Chunhua,Zhang, Yingkai,Diao, Tianning
, p. 4779 - 4786 (2016)
Ni-catalyzed cross-coupling reactions have found important applications in organic synthesis. The fundamental characterization of the key steps in cross-coupling reactions, including C-C bond-forming reductive elimination, represents a significant challenge. Bimolecular pathways were invoked in early proposals, but the experimental evidence was limited. We present the preparation of well-defined (pyridine-pyrrolyl)Ni monomethyl and monophenyl complexes that allow the direct observation of bimolecular reductive elimination to generate ethane and biphenyl, respectively. The sp3-sp3 and sp2-sp2 couplings proceed via two distinct pathways. Oxidants promote the fast formation of Ni(III) from (pyridine-pyrrolyl)Ni-methyl, which dimerizes to afford a bimetallic Ni(III) intermediate. Our data are most consistent with the subsequent methyl coupling from the bimetallic Ni(III) to generate ethane as the rate-determining step. In contrast, the formation of biphenyl is facilitated by the coordination of a bidentate donor ligand.
Transformations of pyridine bases on a nickel-aluminum catalyst
Antonova,Ovchinnikova,Bespalov,Serova,Promonenkov,Ustavshchikov
, p. 280 - 283 (1982)
The electronic structures of some pyridine bases are analyzed by means of 1H and 13C NMR spectroscopic data for substituted pyridines and the calculated bond orders in the pyridine ring. The differences in the chemical bonds in the pyridine ring of isomeric methylpyridines and the carbon-carbon bonds between the ring and the methyl groups in these compounds are in agreement with the experimental data on the thermal stability of the simplest pyridine bases and the gas-phase transformation of the isomeric methylpyridines on an industrial nickel-aluminum catalyst. The possibility of obtaining mono- or dialkylpyridines under these conditions, depending on the structure of the starting pyridine bases, is demonstrated.
Palladium-Catalyzed Methylation of Aryl, Heteroaryl, and Vinyl Boronate Esters
Haydl, Alexander M.,Hartwig, John F.
supporting information, p. 1337 - 1341 (2019/02/26)
A method for the direct methylation of aryl, heteroaryl, and vinyl boronate esters is reported, involving the reaction of iodomethane with aryl-, heteroaryl-, and vinylboronate esters catalyzed by palladium and PtBu2Me. This transformation occurs with a remarkably broad scope and is suitable for late-stage derivatization of biologically active compounds via the boronate esters. The unique capabilities of this method are demonstrated by combining carbon-boron bond-forming reactions with palladium-catalyzed methylation in a tandem transformation.
A mild and efficient H2O2 oxygenation of N-heteroaromatic compounds to the amine N-oxides and KI deoxygenation back to the tertiary amine with hexaphenyloxodiphosphonium triflate
Khodaei, Mohammad Mehdi,Alizadeh, Abdolhamid,Hezarkhani, Hadis Afshar
, p. 1843 - 1849 (2018/07/06)
A mild and efficient method for the oxidation of N-heteroaromatic compounds to the corresponding N-oxides using H2O2 in the presence of hexaphenyloxodiphosphnium triflate (Hendrickson reagent) in EtOH at room temperature was reported. This methodology presented relatively fast and selective reactions to afford the N-oxides in good yields. The reverse reactions, deoxygenation reactions, were also carried out under the same reaction conditions by KI to produce the tertiary amines.
Convenient procedure for the α-methylation of simple pyridines
Broering, Martin,Kleeberg, Christian
scheme or table, p. 3672 - 3682 (2009/04/03)
A convenient and straightforward laboratory procedure is presented for a highly selective mono-α-methylation of pyridines without reactive functional groups. The methylating agent is probably carbon monoxide/dihydrogen generated in situ from a high-boiling alcohol on a metal surface. The reaction is catalyzed by a Raney nickel catalyst at ambient pressure, which renders the protocol practicable in standard organic laboratories. The intrinsically high reaction temperature and long reaction times restrict the application to pyridine derivatives with less reactive substituents. The outcome of the reaction can be rationalized by the assumption of a simple heterogeneous mechanism. Copyright Taylor & Francis Group, LLC.
Inhibitors of cell proliferation, angiogenesis, fertility, and muscle contraction
-
, (2008/06/13)
The invention concerns inhibitors of cell proliferation, angiogenesis, fertility, and muscle contraction, characterized by formula I wherein, X, Y and Z independently represent C or N; ------ is an optional double bond; n is 0 or 1; R1, R2, and R4 independently represent hydrogen, a chemical bond, C1-10 alkyl; C2-10 alkenyl; C2-10 alkinyl; aryl; aryl-C1-10 alkyl; C3-10 heterocyclyl; C5-10 heteroaryl; halo, CF3; NO2; NHC(O)R*, OR, said alkyl, alkenyl, alkinyl, aryl, arylalkyl, heterocyclyl, or heteroaryl being optionally substituted; R3, R5, and R6 independently represent hydrogen, C1-10alkyl; C2-10 alkenyl; C2-10 alkinyl; aryl; aryl-C1-10alkyl; C3-10 heterocyclyl; C5-10 heteroaryl; halo, CF3; NO2; NHC(O)R*, OR, said alkyl, alkenyl, alkinyl, aryl, heterocyclyl, or heteroaryl being optionally substituted; or R5 and R6 together form a 5- or 6-member aryl, heterocyclyl or heteroaryl group; R is hydrogen or C1-6 alkyl; R* is hydrogen, or C1-6 alkyl, or OH, wherein the optional substituents are preferably selected from the group of one to three OH, C1-6 alkyl, halo, NO2, C1-6 alkoxy, and CF3, or a pharmaceutically acceptable salt thereof.
Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease
-
, (2008/06/13)
The invention provides compounds of Formula I: wherein Azabicyclo is These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals in which α7 is known to be involved.
Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease
-
, (2008/06/13)
The invention provides compounds of Formula I: 1where in W is 2These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful to treat diseases or conditions in which α7 is known to be involved.
Substituted 7-aza[2.2.1]bicycloheptanes for the treatment of disease
-
, (2008/06/13)
The invention provides compounds of Formula I: which may be in the form of pharmaceutical acceptable salts or compositions, are useful in treating diseases or conditions in which α7 nicotinic acetylcholine receptors (nAChRs) are known to be involved.
