- Reusable Co-nanoparticles for general and selectiveN-alkylation of amines and ammonia with alcohols
-
A general cobalt-catalyzedN-alkylation of amines with alcohols by borrowing hydrogen methodology to prepare different kinds of amines is reported. The optimal catalyst for this transformation is prepared by pyrolysis of a specific templated material, which is generatedin situby mixing cobalt salts, nitrogen ligands and colloidal silica, and subsequent removal of silica. Applying this novel Co-nanoparticle-based material, >100 primary, secondary, and tertiary amines includingN-methylamines and selected drug molecules were conveniently prepared starting from inexpensive and easily accessible alcohols and amines or ammonia.
- Beller, Matthias,Gawande, Manoj B.,Jagadeesh, Rajenahally V.,Kadam, Ravishankar G.,Li, Xinmin,Ma, Zhuang,Petr, Martin,Zbo?il, Radek,Zhou, Bei
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p. 111 - 117
(2022/01/06)
-
- Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes
-
Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410 nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.
- Cheng, Hanchao,Lam, Tsz-Lung,Liu, Yungen,Tang, Zhou,Che, Chi-Ming
-
supporting information
p. 1383 - 1389
(2020/11/30)
-
- Borane-Trimethylamine Complex as a Reducing Agent for Selective Methylation and Formylation of Amines with CO2
-
We report herein that a borane-trimethylamine complex worked as an efficient reducing agent for the selective methylation and formylation of amines with 1 atm CO2 under metal-free conditions. 6-Amino-2-picoline serves as a highly efficient catalyst for the methylation of various secondary amines, whereas in its absence, the formylation of primary and secondary amines was achieved in high yield with high chemoselectivity. Mechanistic studies suggest that the 6-amino-2-picoline-borane catalytic system operates like an intramolecular frustrated Lewis pair to activate CO2.
- Zhang, Yanmeng,Zhang, He,Gao, Ke
-
supporting information
p. 8282 - 8286
(2021/10/25)
-
- Biobased Spiroimides from Itaconic Acid and Formamides: Molecular Targets for a Novel Synthetic Application of Renewable Chemicals
-
Spiroimides exhibit a wide range of biological activities, such as anticonvulsant, antiarrhythmic, and antihyperglycemic activities. Herein, a novel synthetic application of renewable chemicals, itaconic acid and formamides, is described. Proper exploitation of the reactivity of itaconic acid and formamide allows for the development of an efficient synthetic approach for the production of several new biobased spiroimides, spiro[dihydroquinolin-2-one-succinimides] and spiro[indolin-2-one-glutarimides], in excellent overall yields (up to 98%).
- Hornink, Milene Macedo,Lopes, Alice Uva,Andrade, Leandro Helgueira
-
supporting information
p. 296 - 308
(2020/11/09)
-
- Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol
-
Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.
- Sarki, Naina,Goyal, Vishakha,Tyagi, Nitin Kumar,Puttaswamy,Narani, Anand,Ray, Anjan,Natte, Kishore
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p. 1722 - 1729
(2021/04/19)
-
- Catalyst-Free Electrosynthesis of Benzimidazolones through Intramolecular Oxidative C?N Coupling
-
The electrochemical synthesis of N, N’-disubstituted benzimidazolones from ureas through an intramolecular anodic dehydrogenative N?H/C?H coupling has been developed. The reaction undergoes under the undivided electrolysis conditions and obviates the need for any catalysts and chemical oxidants. (Figure presented.).
- Li, Jiang-Sheng,Yang, Pan-Pan,Xie, Xin-Yun,Jiang, Si,Tao, Li,Li, Zhi-Wei,Lu, Cui-Hong,Liu, Wei-Dong
-
supporting information
p. 1977 - 1981
(2020/04/20)
-
- P(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate
-
The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
- Li, Gen,Qin, Ziyang,Radosevich, Alexander T.
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p. 16205 - 16210
(2020/10/26)
-
- Electrosynthesis of Dihydropyrano[4,3-b]indoles Based on a Double Oxidative [3+3] Cycloaddition
-
Oxidative [3+3] cycloadditions offer an efficient route for six-membered-ring formation. This approach has been realized based on an electrochemical oxidative coupling of indoles/enamines with active methylene compounds followed by tandem 6π-electrocyclization leading to the synthesis of dihydropyrano[4,3-b]indoles and 2,3-dihydrofurans. The radical–radical cross-coupling of the radical species generated by anodic oxidation combined with the cathodic generation of the base from O2 allows for mild reaction conditions for the synthesis of structurally complex heterocycles.
- Choi, Subin,Park, Cheol-Min,Park, Jinhwi,Sim, Jeongwoo,Yu, Eunsoo
-
supporting information
p. 11886 - 11891
(2020/05/22)
-
- Visible-Light-Enabled Direct Decarboxylative N-Alkylation
-
The development of efficient and selective C?N bond-forming reactions from abundant feedstock chemicals remains a central theme in organic chemistry owing to the key roles of amines in synthesis, drug discovery, and materials science. Herein, we present a dual catalytic system for the N-alkylation of diverse aromatic carbocyclic and heterocyclic amines directly with carboxylic acids, by-passing their preactivation as redox-active esters. The reaction, which is enabled by visible-light-driven, acridine-catalyzed decarboxylation, provides access to N-alkylated secondary and tertiary anilines and N-heterocycles. Additional examples, including double alkylation, the installation of metabolically robust deuterated methyl groups, and tandem ring formation, further demonstrate the potential of the direct decarboxylative alkylation (DDA) reaction.
- Arman, Hadi D.,Dang, Hang T.,Haug, Graham C.,Larionov, Oleg V.,Nguyen, Viet D.,Nguyen, Vu T.,Vuong, Ngan T. H.
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supporting information
p. 7921 - 7927
(2020/04/10)
-
- Highly Efficient Binuclear Copper-catalyzed Oxidation of N,N-Dimethylanilines with O2
-
A binuclear copper-salicylate complex, [Cu(Sal)2(NCMe)]2 (Sal=salicylate), was found to be an active catalyst for the oxidation of N,N-dimethylanilines by O2, affording the corresponding N-methyl-N-phenylformamides as major products. The reactions were carried out with a O2 balloon and the S/C (substrate/catalyst ratio) of the model reaction could be up to 1×105, providing a practical and highly efficient catalytic protocol for accessing N-methyl-N-phenylformamides.
- Liu, Yuxia,Yan, Yonggang,Xue, Dong,Wang, Zhongfu,Xiao, Jianliang,Wang, Chao
-
p. 2221 - 2225
(2020/03/23)
-
- Esterification of Tertiary Amides: Remarkable Additive Effects of Potassium Alkoxides for Generating Hetero Manganese–Potassium Dinuclear Active Species
-
A catalyst system of mononuclear manganese precursor 3 combined with potassium alkoxide served as a superior catalyst compared with our previously reported manganese homodinuclear catalyst 2 a for esterification of not only tertiary aryl amides, but also tertiary aliphatic amides. On the basis of stoichiometric reactions of 3 and potassium alkoxide salt, kinetic studies, and density functional theory (DFT) calculations, we clarified a plausible reaction mechanism in which in situ generated manganese–potassium heterodinuclear species cooperatively activates the carbonyl moiety of the amide and the OH moiety of the alcohols. We also revealed details of the reaction mechanism of our previous manganese homodinuclear system 2 a, and we found that the activation free energy (ΔG≠) for the manganese–potassium heterodinuclear complex catalyzed esterification of amides is lower than that for the manganese homodinuclear system, which was consistent with the experimental results. We further applied our catalyst system to deprotect the acetyl moiety of primary and secondary amines.
- Akiyama, Shoko,Himo, Fahmi,Hirai, Takahiro,Katayama, Shoichiro,Kato, Daiki,Mai, Binh Khanh,Mashima, Kazushi,Nagae, Haruki
-
-
- Catalytic Hydrogenation of Carboxamides with a Bifunctional Cp Ru Catalyst Bearing an Imidazol-2-ylidene with a Protic Aminoethyl Side Chain
-
Synthesis of a Cp Ru complex bearing an NH 2 -functionalized N -heterocyclic carbene (C-N H) was achieved by treatment of CpRuBr(isoprene) with an equimolar amount of a silver complex, which was generated from Ag 2 O and 1-(2-aminoethyl)-3-methylimidazolium bromide, in CH 3 CN at room temperature. The new CpRuBr(C-N H) complex showed a higher catalytic performance than the related CpRuCl(P-N H) and CpRuCl(N-N H) complexes. In the reaction of N -arylcarboxamides, the amine products were obtained in satisfactory yields under mild temperature conditions.
- Ikariya, Takao,Kawano, Teruhiro,Kayaki, Yoshihito,Watari, Ryo
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p. 2542 - 2547
(2019/06/08)
-
- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
-
The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
-
-
- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
-
The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
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p. 14627 - 14635
(2019/12/02)
-
- Highly selective hydrogenation of amides catalysed by a molybdenum pincer complex: Scope and mechanism
-
A series of molybdenum pincer complexes has been shown for the first time to be active in the catalytic hydrogenation of amides. Among the tested catalysts, Mo-1a proved to be particularly well suited for the selective C-N hydrogenolysis of N-methylated formanilides. Notably, high chemoselectivity was observed in the presence of certain reducible groups including even other amides. The general catalytic performance as well as selectivity issues could be rationalized taking an anionic Mo(0) as the active species. The interplay between the amide CO reduction and the catalyst poisoning by primary amides accounts for the selective hydrogenation of N-methylated formanilides. The catalyst resting state was found to be a Mo-alkoxo complex formed by reaction with the alcohol product. This species plays two opposed roles-it facilitates the protolytic cleavage of the C-N bond but it encumbers the activation of hydrogen.
- Leischner, Thomas,Artús Suarez, Lluis,Spannenberg, Anke,Junge, Kathrin,Nova, Ainara,Beller, Matthias
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p. 10566 - 10576
(2019/12/02)
-
- Iron-Catalyzed Regioselective α-C-H Alkylation of N-Methylanilines: Cross-Dehydrogenative Coupling between Unactivated C(sp3)-H and C(sp3)-H Bonds via a Radical Process
-
The iron-catalyzed α-C-H alkylation of N-methylanilines without any directing group by cross-dehydrogenative coupling between unactivated C(sp3)-H and C(sp3)-H bonds has been established for the first time, which provides a good complement to C(sp3)-H activation reactions and expands the field of Fe-catalyzed C-H functionalizations. Many different C(sp3)-H bonds in cyclic alkanes, cyclic ethers, and toluene derivatives can be used as coupling partners. Mechanistic investigations including the radical reaction process, the main role of various reagents, and the kinetic isotope effect experiment were also described.
- Li, Ze-Lin,Sun, Kang-Kang,Wu, Peng-Yu,Cai, Chun
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p. 6830 - 6839
(2019/06/14)
-
- Selective formylation or methylation of amines using carbon dioxide catalysed by a rhodium perimidine-based NHC complex
-
Carbon dioxide can play a vital role as a sustainable feedstock for chemical synthesis. To be viable, the employed protocol should be as mild as possible. Herein we report a methodology to incorporate CO2 into primary, secondary, aromatic or alkyl amines catalysed by a Rh(i) complex bearing a perimidine-based NHC/phosphine pincer ligand. The periminide-based ligand belongs to a class of 6-membered NHC ligand accessed through chelate-assisted double C-H activation. N-Formylation and -methylation of amines were performed using a balloon of CO2, and phenylsilane as the reducing agent. Product selectivity between formylated and methylated products was tuned by changing the solvent, reaction temperature and the quantity of phenylsilane used. Medium to excellent conversions, as well as tolerance to a range of functional groups, were achieved. Stoichiometric reactions with reactants employed in catalysis and time course studies suggested that formylation and methylation reactions of interest begin with hydrosilylation of CO2 followed by reaction with amine substrates.
- Lam, Raphael H.,McQueen, Caitlin M. A.,Pernik, Indrek,McBurney, Roy T.,Hill, Anthony F.,Messerle, Barbara A.
-
supporting information
p. 538 - 549
(2019/02/14)
-
- Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow
-
Selective N-monomethylation of anilines has been achieved under continuous flow conditions using dimethyl carbonate as a green methylating agent in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene. Our methodology takes advantage of the expanded process windows available in the continuous flow regime to safely induce monomethylation in superheated solvents at high pressure. We propose selective N-monomethylation is achieved via an in situ protection-deprotection pathway, which is supported by the observed reactivities of several putative reaction intermediates. The robust and scalable method was applicable to a broad range of primary aniline substrates including ortho-, meta-, and para-substituted anilines, as well as electron-rich and electron-deficient anilines. The synthetic precursor of diazepam, 5-chloro-2-(methylamino)benzophenone, was selectively synthesized under our optimized conditions.
- Seo, Hyowon,Bédard, Anne-Catherine,Chen, Willie P.,Hicklin, Robert W.,Alabugin, Alexander,Jamison, Timothy F.
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p. 3124 - 3128
(2017/12/11)
-
- Novel nonmetal catalytic bidirectional selective reduction method of tertiary aromatic amide
-
The invention relates to a novel effective bidirectional selective environment-friendly method for hydrosilation reduction of tertiary aromatic amide and an organic silicon reagent. The method comprises the following steps: selecting a nonmetal catalytic system, and selectively preparing a secondary or tertiary organic amine compound by successively catalyzing tertiary aromatic amide and cheap PHMS or triethoxysilane under a mild condition. By adopting the method, the bidirectional selective reduction of the tertiary aromatic amide is realized by innovatively utilizing an electronic effect and steric hindrance difference of an organic silicon reagent at first time, so that a brand new strategy is provided for the reduction of amide and derivative of the amide, the defects of the traditional method that the substrate functional group is poor in compatibility, the production cost is high and the like can be overcome, and the application prospect of the amine compound prepared in industrial production or laboratory is promising.
- -
-
Paragraph 0038; 0039; 0040; 0041
(2017/10/22)
-
- Efficient Cobalt-Catalyzed Methylation of Amines Using Methanol
-
The methylation of amines using methanol is a promising route to synthesize N-methylamines, and the development of cheap and efficient catalytic system for this reaction is of great significance. Herein, we reported a cobalt (Co)-based catalytic system, which was in situ formed from commercially available Co precursor and a tetradentate phosphine ligand P(CH2CH2PPh2)3 combined with K3PO4. This catalystic system was very effective for the selective production of dimethylated products from aliphatic amines and monomethylated ones from aromatic amines. The reaction mechanism was further investigated by control and isotope labelling experiments. (Figure presented.).
- Liu, Zhenghui,Yang, Zhenzhen,Yu, Xiaoxiao,Zhang, Hongye,Yu, Bo,Zhao, Yanfei,Liu, Zhimin
-
supporting information
p. 4278 - 4283
(2017/10/23)
-
- NOVEL PYRIDAZONES AND TRIAZINONES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
-
The invention provides novel compounds having the general formula wherein R1, R2, R3, X and a are as described in the description and in the claims, as well as or pharmaceutically acceptable salts thereof. The invention also contains compositions including the compounds and methods of using the compounds.
- -
-
Page/Page column 25
(2016/02/29)
-
- Base-oxidant promoted metal-free N-demethylation of arylamines
-
A metal-free oxidative N-demethylation of arylamines with triethylamine as a base and tert-butyl hydroperoxide (TBHP) as oxidant is reported in this paper. The reaction is general, practical, inexpensive, non-toxic, and the method followed is environmentally benign, with moderate to good yields. [Figure not available: see fulltext.]
- Botla, Vinayak,Barreddi, Chiranjeevi,Daggupati, Ramana V,Malapaka, Chandrasekharam
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p. 1469 - 1473
(2016/09/19)
-
- Methanol dehydrogenation by iridium N-heterocyclic carbene complexes
-
A series of homogeneous iridium bis(N-heterocyclic carbene) catalysts are active for three transformations involving dehydrogenative methanol activation: acceptorless dehydrogenation, transfer hydrogenation, and amine monoalkylation. The acceptorless dehydrogenation reaction requires base, yielding formate and carbonate, as well as 2-3 equivalents of H2. Of the few homogeneous systems known for this reaction, our catalysts tolerate air and employ simple ligands. Transfer hydrogenation of ketones and imines from methanol is also possible. Finally, N-monomethylation of anilines occurs through a borrowing hydrogen reaction. Notably, this reaction is highly selective for the monomethylated product.
- Campos, Jesús,Sharninghausen, Liam S.,Manas, Michael G.,Crabtree, Robert H.
-
p. 5079 - 5084
(2015/06/16)
-
- Isotope effect profiles in the N-demethylation of N,N-dimethylanilines: A key to determine the pKa of nonheme Fe(III)-OH complexes
-
N-demethylation of N,N-dimethylanilines promoted by [(N4Py)FeIVO]2+ occurs by an electron transfer-proton transfer (ET-PT) mechanism with a rate determining PT step. From the bell-shaped curve of the KDIE profile it has been estimated that the pKa of [(N4Py)FeIII-OH]2+ is 9.7.
- Barbieri, Alessia,De Gennaro, Martina,Di Stefano, Stefano,Lanzalunga, Osvaldo,Lapi, Andrea,Mazzonna, Marco,Olivo, Giorgio,Ticconi, Barbara
-
p. 5032 - 5035
(2015/03/30)
-
- NOVEL CATALYSTS
-
The present invention provides novel compounds and ligands that are useful in transition metal catalyzed cross-coupling reactions. For example, the compounds and ligands of the present invention are useful in palladium or gold catalyzed cross-coupling reactions.
- -
-
Page/Page column 66
(2012/06/01)
-
- A facile protocol for the synthesis of mono-N-methyl anilines via formimidate intermediates
-
A general procedure for the preparation of mono-N-methyl anilines has been developed with excellent yields. This protocol relies on a NaBH3(OAc) reduction of formimidate intermediates that are quantitatively generated by treatment of primary substituted anilines with triethyl orthoformate under the catalysis of MCM-41-SO3H mesoporous zeolite. The newly developed procedure was facile, efficient, and environmentally benign.
- Sun, Nan,Wang, Shuai,Mo, Weimin,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
-
experimental part
p. 7142 - 7148
(2010/09/14)
-
- A highly versatile catalyst system for the cross-coupling of aryl chlorides and Amines
-
The syntheses of 2-(di-tertbutylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74%), and their application in BuchwaldHartwig amination, are reported. In combination with [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2, these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)2, PdCl2, [PdCl2(cod)] (cod = 1,5-cyclooctadiene), [PdCl 2(MeCN)2], or [Pd2(dba)3] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2 with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortto-dimethylamino fragment. Given current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross-coupling of aryl chlorides and amines
- Lundgren, Rylan J.,Sappong-Kumankumah, Antonia,Stradiotto, Mark
-
experimental part
p. 1983 - 1991
(2010/07/03)
-
- N-Demethylation of N,N-Dimethylanilines by the benzotriazole N-Oxyl radical: Evidence for a two-step electron transfer-proton transfer mechanism
-
"Chemical Equation Presented" The reaction of the benzotriazole N-oxyl radical (BTNO) with a series of 4-X-N,N-dimethylanilines (X = CN, CF 3, CO2CH2CH3, CH3, OC6H5, OCH3) has been investigated in CH 3CN. Product analysis shows that the radical, 4-X-C6H 4N(CH3)CH2·, is first formed, which can lead to the N-demethylated product or the product of coupling with BTNO. Reaction rates were found to increase significantly by increasing the electron-donating power of the aryl substituents (p+ = -3.8). With electron-donating substituents (X = CH3, OC6H5, OCH3), no intermolecular deuterium kinetic isotope effect (DKIE) and a substantial intramolecular DKIE are observed. With electron-withdrawing substituents (X = CN, CF3, CO2CH2CH 3), substantial values of both intermolecular and intramolecular DKIEs are observed. These results can be interpreted on the basis of an electron-transfer mechanism from the N,N-dimethylanilines to the BTNO radical followed by deprotonation of the anilinium radical cation (ET-PT mechanism). By applying the Marcus equation to the kinetic data for X = CH3, OC 6H5, OCH3 (rate-determining ET), a reorganization energy for the ET reaction was determined (λ BTNO/DMA= 32.1 kcal mol- 1). From the self-exchange reorganization energy for the BTNO/BTNO- couple, a self-exchange reorganization energy value of 31.9 kcal mol-1 was calculated for the DMA·+/DMA couple.
- Baciocchi, Enrico,Bietti, Massimo,Lanzalunga, Osvaldo,Lapi, Andrea,Raponi, Daniele
-
supporting information; experimental part
p. 1378 - 1385
(2010/06/11)
-
- Selective monomethylation of anilines by Cu(OAc)2-promoted cross-coupling with MeB(OH)2
-
N-Methylanilines are readily synthesized in high yields through the copper(ll)-promoted coupling of anilines and methylboronic acid. This method represents a new approach for the selective monomethylation of anilines, and it is the first reported example
- Gonzalez, Israel,Mosquera, Jesus,Guerrero, Cesar,Rodriguez, Ramon,Cruces, Jacobo
-
supporting information; experimental part
p. 1677 - 1680
(2009/09/06)
-
- Identification and characterization of amino-piperidinequinolones and quinazolinones as MCHr1 antagonists
-
Several potent, functionally active MCHr1 antagonists derived from quinolin-2(1H)-ones and quinazoline-2(1H)-ones have been synthesized and evaluated. Pyridylmethyl substitution at the quinolone 1-position results in derivatives with low-nM binding potency and good selectivity with respect to hERG binding.
- Blackburn, Christopher,LaMarche, Matthew J.,Brown, James,Che, Jennifer Lee,Cullis, Courtney A.,Lai, Sujen,Maguire, Martin,Marsilje, Thomas,Geddes, Bradley,Govek, Elizabeth,Kadambi, Vivek,Doherty, Colleen,Dayton, Brian,Brodjian, Sevan,Marsh, Kennan C.,Collins, Christine A.,Kym, Philip R.
-
p. 2621 - 2627
(2007/10/03)
-
- Electron-transfer mechanism in the N-demethylation of N,N-dimethylanilines by the phthalimide-N-oxyl radical
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The reactivity of the phthalimide N-oxyl radical (PINO) toward the N-methyl C-H bond of a number of 4-X-substituted N,N-dimethylanilines (X = OMe, OPh, CF3, CO2Et, CN) has been investigated by product and kinetic analysis. PINO was generated in CH3CN by reaction of N-hydroxyphthalimide (NHPI) with Pb(OAc)4 or, for the kinetic study of the most reactive substrates (X = OMe, OPh), with tert-butoxyl radical produced by 266 nm laser flash photolysis of di-tert-butyl peroxide. The reaction was found to lead to the N-demethylation of the N,N-dimethylaniline with a rate very sensitive to the electron donating power of the substituent (ρ+ = -2.5) as well as to the oxidation potential of the substrates. With appropriately deuterated N,N-dimethylanilines the intermolecular and intramolecular deuterium kinetic isotope effects (DKIEs) were measured for some substrates (X = OMe, CO2Et, CN) with the following results. First, intramolecular DKIE [(kH/kD) intra] was found to be always different and higher than intermolecular DKIE [(kH/kD)inter]; second, no intermolecular DKIE [(kH/kD)inter = 1] was observed for X = OMe, whereas substantial values of (kH/k D)inter were exhibited by X = CO2Et (4.8) and X = CN (5.8). These results, while are incompatible with a single step hydrogen atom transfer from the N-C-H bond to the N-oxyl radical, as proposed for the reaction of PINO with benzylic C-H bonds, can be nicely interpreted on the basis of a two-step mechanism involving a reversible electron transfer from the aniline to PINO leading to an anilinium radical cation, followed by a proton-transfer step that produces an α-amino carbon radical. In line with this conclusion the reactivity data exhibited a good fit with the Marcus equation and a λ value of 37.6 kcal mol-1 was calculated for the reorganization energy required in this electron-transfer process. From this value, a quite high reorganization energy (> 60 kcal mol-1) is estimated for the PINO/NHPI(-H)- self-exchange reaction. It is suggested that the N-demethylated product derives from the reaction of the α-amino carbon radical with PINO to form either a cross-coupling product or an α-amino carbocation. Both species may react with the small amounts of H2O present in the medium to form a carbinolamine that, again by hydrolysis, can be eventually converted into the N-demethylated product.
- Baciocchi, Enrico,Bietti, Massimo,Gerini, Maria Francesca,Lanzalunga, Osvaldo
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p. 5144 - 5149
(2007/10/03)
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- Synthesis of primary amines and N-methylamines by the electrophilic amination of Grignard reagents with 2-imidazolidinone O-sulfonyloxime
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2-Imidazolidinone O-sulfonyloxime reacts with various aryl and alkyl Grignard reagents as an electrophilic amination reagent, giving N-alkylated imines. The resulting imines are transformed to primary amines and N-methyl secondary amines by hydrolysis with CsOH and LiAlH4 reduction, respectively.
- Kitamura, Mitsuru,Chiba, Shunsuke,Narasaka, Koichi
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p. 1063 - 1070
(2007/10/03)
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- Isotope-effect profiles in the oxidative N-demethylation of N,N-dimethylanilines catalysed by lignin peroxidase and a chemical model
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Lignin peroxidase catalyses the oxidative N-demethylation of ring-substituted N,N-dimethylanilines by an electron-transfer mechanism whereby an anilinium radical cation is formed which is then deprotonated by the enzyme. Information on the nature of the basic centre which deprotonates the radical cation has been obtained by determining the KDIE profile (plot of kH/kD vs. the pKa of the aniline radical cations) for a number of ring-substituted N,N- bis(dideuteriomethyl)-anilines. From the bell-shaped curve it has been estimated that the pKa of the proton-abstracting base is about 7. Interestingly, almost the same value has been obtained when the same type of study has been carried out using a water-soluble model compound: 5,10,15,20-tetraphenyl-21H,23H-porphine-p,p′,p″, p?-tetrasulfonic acid iron(III) chloride. This is a strong indication that the radical cation is deprotonated by the same species in the enzymatic and in the chemical reactions. It is suggested that this species is the reduced iron-oxo complex.
- Baciocchi, Enrico,Gerini, M. Francesca,Lanzalunga, Osvaldo,Lapi, Andrea,Lo Piparo, Maria Grazia,Mancinelli, Simona
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p. 2305 - 2310
(2007/10/03)
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- Oxidative N-demethylation of N,N-dimethylanilines catalysed by lignin peroxidase: A mechanistic insight by a kinetic deuterium isotope effect study
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Lignin peroxidase can catalyse the N-demethylation of N,N- dimethylanilines by an electron transfer mechanism, where the deprotonation of the intermediate radical cation is also an enzymatic process.
- Baciocchi, Enrico,Gerini, Maria Francesca,Lanzalunga, Osvaldo,Lapi, Andrea,Mancinelli, Simona,Mencarelli, Paolo
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p. 393 - 394
(2007/10/03)
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- N-methylanilines from benzylic azides
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Benzylic azides are converted into N-methylanilines efficiently in the presence of a Bronsted or Lewis acid and Et3SiH. The combination of SnCl4/Et3SiH and 4-n-butylbenzyl azide appears to form an aminodiazonium trichlorostannate(II), which undergoes the rearrangement to an iminium salt that is then reduced to N-methyl-4-n-butylaniline by Et3SiH.
- Lopez, Francisco J.,Nitzan, Dov
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p. 2071 - 2074
(2007/10/03)
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- Synthesis and Biological Activity of a Series of Diaryl-Substituted α-Cyano-β-hydroxypropenamides, a New Class of Anthelmintic Agents
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A series of α-cyano-β-hydroxypropenamides was prepared and tested for anthelmintic activity. α-Cyano-β-hydroxy-N--3-propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana.In sheep trials, 1 caused 100percent reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta.Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated.Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.
- Sjogren, Eric B.,Rider, Michael A.,Nelson, Peter H.,Bingham, Stanford,Poulton, Anthony L.,et al.
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p. 3295 - 3301
(2007/10/02)
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