- Pyridine mediated transition-metal-free direct alkylation of anilines using alcohols: via borrowing hydrogen conditions
-
Herein, we report pyridine and other similar azaaromatics as efficient biomimetic hydrogen shuttles for a transition-metal-free direct N-alkylation of aryl and heteroaryl amines using a variety of benzylic and straight chain alcohols. Mechanistic studies including deuterium labeling and the isolation of dihydro-intermediates of the benzannulated pyridine confirmed the role of pyridine and a borrowing hydrogen process operating in these reactions. In addition, we have extended this methodology for the development of dehydrogenative synthesis of quinolines and indoles, as well as the transfer hydrogenation of ketones. This journal is
- Pothikumar, Rajagopal,Bhat, Venugopal T,Namitharan, Kayambu
-
supporting information
p. 13607 - 13610
(2020/11/17)
-
- Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters
-
A new three-component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2-pyridinyl (Py) directing group, is described. The N-Py-amide substrates are readily prepared from carboxylic acids and PyNH2, and the resulting N-Py-1-arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN-Py group with HCl. The 1-aryl-1-chloroalkane products allow substitution and cross-coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py-NH2 by-product can be recycled.
- Ronson, Thomas O.,Renders, Evelien,Van Steijvoort, Ben F.,Wang, Xubin,Wybon, Clarence C. D.,Prokopcová, Hana,Meerpoel, Lieven,Maes, Bert U. W.
-
supporting information
p. 482 - 487
(2019/01/04)
-
- Mesoionic pyrido[1,2-a]pyrimidinones: A novel class of insecticides inhibiting nicotinic acetylcholine receptors
-
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we report the discovery, evolution, and preparation of this class of chemistry. Our efforts in structure–activity relationship elucidation and biological activity evaluation are also presented.
- Zhang, Wenming,Holyoke, Caleb W.,Barry, James,Leighty, Robert M.,Cordova, Daniel,Vincent, Daniel R.,Hughes, Kenneth A.,Tong, My-Hanh T.,McCann, Stephen F.,Xu, Ming,Briddell, Twyla A.,Pahutski, Thomas F.,Lahm, George P.
-
p. 5444 - 5449
(2016/11/11)
-
- A catalyst system, copper/ N -methoxy-1 H -pyrrole-2-carboxamide, for the synthesis of phenothiazines in poly(ethylene glycol)
-
A copper/N-methoxy-1H-pyrrole-2-carboxamide catalyst system has been established for the preparation of phenothiazines in good yields by two routes, starting from 2-iodoanilines and 2-bromobenzenethiol and from aryl ortho-dihalides and o-aminobenzenethiols, by conducting the reaction at 90 °C in poly(ethylene glycol)-100 (PEG-100). In addition, the catalyst system was useful for promoting direct arylation of various aryl amines, aliphatic amines, and aqueous ammonia. The simple experimental operation, low loading of catalyst system together with the use of green solvent, makes it attractive for the versatile syntheses of phenothiazines and various amines.
- Huang, Manna,Hou, Jianying,Yang, Ruiqiao,Zhang, Liting,Zhu, Xinhai,Wan, Yiqian
-
supporting information
p. 3356 - 3364
(2015/02/02)
-
- Use of primary amines for the selective n-alkylation of anilines by a reusable heterogeneous catalyst
-
Traditionally, anilines can be alkylated with reactive alkyl halides but now more safe reagents such as alcohols or even amines can be used. To overcome the limits of homogeneous catalysis for aniline N-alkylation, we have developed a protocol that employs simple Pd/C as a heterogeneous catalyst under microwave dielectric heating. The process, based on the easy Pd-mediated oxidation of primary amines to imines followed by aniline addition, is characterized by a high atom economy as ammonia is the only other product of the reaction. This kind of aniline alkylation with amines has been carried out both in ionic liquid medium using [bmim]PF6 or in a more traditional solvent such as THF where the catalyst could be successfully recycled more times. The reusability of the catalyst was further confirmed by using material recycled from the amination in a standard alkene hydrogenation without loss of efficiency. Georg Thieme Verlag Stuttgart New York.
- Linciano, Pasquale,Pizzetti, Marianna,Porcheddu, Andrea,Taddei, Maurizio
-
p. 2249 - 2254
(2013/11/06)
-
- A recyclable Cu-catalyzed C-N coupling reaction in water and its application to synthesis of imidazo[1,2-a]quinoxaline
-
Polystyrene-supported pyrrole-2-carbohydrazide (PSP) was synthesized and combined with CuI to make up a recyclable heterogeneous catalytic system for Ullmann-type C-N coupling reaction in water. In which, a variety of functionalized aryl halides animated efficiently with anilines, benzylamine, aliphatic amines, and imidazole. its preliminary application resulted in a more practical synthesis of imidazo[1,2-a]quinoxaline.
- Huang, Liye,Yu, Ruina,Zhu, Xinhai,Wan, Yiqian
-
supporting information
p. 8974 - 8977
(2013/09/23)
-
- Cationic iridium-catalyzed enantioselective activation of secondary sp 3 C-H bond adjacent to nitrogen atom
-
A cationic Ir(I)-tolBINAP complex catalyzed an enantioselective C-C bond formation, which was initiated by secondary sp3 C-H bond cleavage adjacent to nitrogen atom. A wide variety of 2-(alkylamino)pyridines and alkenes were selectively transformed into the corresponding chiral amines with moderate to almost perfect enantiomeric excesses. Alkynes were also investigated as coupling partners. The effect of alkyl structure in substrates and directing groups were studied. This transformation represents the first example of a highly enantioselective C-H bond activation of a methylene group, not at allylic or benzylic position.
- Pan, Shiguang,Matsuo, Yusuke,Endo, Kohei,Shibata, Takanori
-
p. 9009 - 9015
(2012/10/30)
-
- Efficient catalytic aryl amination of bromoarenes using 3-iminophosphine palladium(II) chloride
-
While pursuing the development of new hydroamination catalysts, a 3-iminophosphine palladium(II) chloride complex [(3IP)PdCl2] was synthesized that has subsequently proven to be an effective precatalyst for the aryl amination of bromoarenes. This (3IP)PdCl2 complex has been utilized in the catalytic aryl amination of both bromobenzene and bromopyridine derivatives, specifically yielding excellent activity in coupling reactions involving bromobenzene, 4-bromotoluene, and 2-bromopyridine. Using a standard set of catalytic conditions, many alkyl and aryl amines have been investigated as coupling partners in the aryl amination of bromoarenes. In general, secondary alkyl amines and ortho-substituted anilines proved to be the best substrates for this reaction, commonly giving quantitative conversion to products, while primary amines and other anilines gave only poor to moderate results. Catalytic screening data, product yields, and full characterization of isolated products are included.
- Samblanet, Danielle C.,Schmidt, Joseph A. R.
-
p. 7 - 18,12
(2012/12/12)
-
- A facile N-monoalkylation of aminopyridines
-
The N-monoalkylation of 2- or 3-aminopyridines by a carboxylic acid and sodium borohydride afforded the corresponding alkylaminopyridine under mild conditions in good yields. N-Alkylaminopyridines are important intermediate for preparing N-containing heterocycles, such as flytrap aminopyridinium-based anion hosts and pharmaceuticals.
- Tian, Zhongzhen,Li, Dongmei,Jiang, Zhaoxing,Li, Zhong
-
p. 628 - 629,2
(2020/07/30)
-
- Copper-mediated aryl amination: In situ generation of an active copper(I) species
-
We have developed novel conditions for copper-mediated aryl amination by using a combination of easy-to-handle and inexpensive Cu(OAc) 2·H2O and phenylhydrazine. Georg Thieme Verlag Stuttgart . New York.
- Komori, Takashi,Satoh, Nobuhiro,Yokoshima, Satoshi,Fukuyama, Tohru
-
experimental part
p. 1859 - 1862
(2011/09/15)
-
- G-PROTEIN-CONJUGATED RECEPTOR AGONIST
-
Disclosed is a novel aralkyl carboxylic acid compound which has an agonistic activity on GPR-120 and/or GPR-40, particularly GPR-120, and is therefore useful as an appetite regulator, an anti-obesity agent, a therapeutic agent for diabetes, a pancreatic beta differentiating cell growth enhancer, a therapeutic agent for metabolic syndrome, a therapeutic agent for a gastrointestinal disease, a therapeutic agent for a neuropathy, a therapeutic agent for a mental disorder, a therapeutic agent for a pulmonary disease, a therapeutic agent for a pituitary hormone secretion disorder or a lipid flavoring/seasoning agent. The aralkyl carboxylic acid compound is represented by the general formula (I). (I) wherein the ring Q represents a pyridyl or the like; R1 represents a C1-6 alkyl group or the like; R2 represents a hydrogen atom, a C1-4 alkyl group or a C1-4 alkoxy group; m and n independently represent an integer of 1 to 5; and X represents an oxygen atom, a sulfur atom or - NR3- [wherein R3 represents a hydrogen atom or a C1-4 alkyl group].
- -
-
Page/Page column 30-31
(2010/03/02)
-
- Selective iridium-catalyzed alkylation of (hetero)aromatic amines and diamines with alcohols under mild reaction conditions
-
A P,N-ligand-coordinated iridium complex has been employed as an efficient catalyst for the selective monoalkylation of (hetero) aromatic amines with alcohols. A significant improvement of this alkylation method has been achieved, such that it can be performed at a temperature of 70°C and with catalyst loadings as low as 0.1 mol% Ir, while still affording excellent yields of secondary amines. Furthermore, the high selectivity of this catalyst for the monoalkylation of aromatic amino functions has been successfully exploited for the alkylation of diamines in both symmetric and non-symmetric fashions, providing a novel and very efficient synthetic tool for the preparation of N,N'-dialkylated aromatic diamines.
- Blank, Benoit,Michlik, Stefan,Kempe, Rhett
-
experimental part
p. 3790 - 3799
(2009/12/05)
-
- An efficient method for the selective iridium-catalyzed monoalkylation of (hetero)aromatic amines with primary alcohols
-
An efficient multi-gram scale synthesis protocol of a variety of P,N ligands is described. The synthesis is achieved in a two-step reaction. First, the amine is deprotonated and subsequently the chlorophosphine is added to yield the corresponding P,N ligand. Deprotonation of the amine is normally achieved with n-BuLi at low temperature, but for the preparation of ligands with a 2,2′-dipyridylamino backbone and phosphines with a high steric demand KH has to be employed in combination with reaction temperatures of 110°C for the salt metathesis step. The reaction of two equivalents of a selected P,N ligand with one equivalent of the iridium complex [IrCl(cod)]2 (cod=1,5-cyclooctadiene) affords P,N ligand-coordinated iridium complexes in quantitative yield. X-Ray single crystal structure analysis of one of these complexes reveals a monomeric five-coordinated structure in the solid state. The iridium complexes were used to form catalysts for the N-alkylation of aromatic amines with alcohols. The catalyst system was optimized by studying 8 different P,N ligands, 9 different solvents and 14 different bases. Systematic variation of the substrate to base and the amine to alcohol ratios as well as the catalyst loading led to optimized catalytic reaction conditions. The substrate scope of the developed catalytic protocol was shown by synthesizing 20 different amines of which 12 could be obtained in isolated yields higher than 90%. A new efficient catalyst system for the selective monoalkylation of primary aromatic and heteroaromatic amines with primary aromatic, heteroaromatic as well as aliphatic alcohols has been established. The reaction proceeds with rather moderate catalyst loadings.
- Blank, Benoit,Madalska, Martyna,Kempe, Rhett
-
supporting information; experimental part
p. 749 - 758
(2009/04/10)
-
- A mild, catalyst-free synthesis of 2-aminopyridines
-
Alkylation of 2-mercaptopyridine with 1,2-dibromoethane affords a cyclic dihydrothiazolopyridinium salt that can serve as a precursor of 2-aminopyridines. Its reaction with primary or secondary amines, either neat or in DMSO, under mild conditions gives the title compounds.
- Poola, Bhaskar,Choung, Wonken,Nantz, Michael H.
-
p. 10798 - 10801
(2008/12/23)
-
- A mild inter- and intramolecular amination of aryl halides with a combination of CuI and CsOAc
-
A unique combination of CuI and CsOAc was found to catalyze aryl amination under mild conditions. The reaction takes place at room temperature or at 90 °C with broad functional group compatibility. The intramolecular reaction was able to form five-, six-, and seven-membered rings with various protecting groups on the nitrogen atom. The scope of the intermolecular amination, as well as its applications to unsymmetrical N,N′-dialkylated phenylenediamines, was investigated.
- Kubo, Tetsuji,Katoh, Chiharu,Yamada, Ken,Okano, Kentaro,Tokuyama, Hidetoshi,Fukuyama, Tohru
-
experimental part
p. 11230 - 11236
(2009/04/11)
-
- Synthesis of nitro N,N′-dipyridinylamines via oxidative nucleophilic substitution of hydrogen
-
The amination of 3-nitropyridines with aromatic amides generated from various aminopyridine derivatives proceeded unexpectedly in the position para to the nitro group, giving the oxidative nucleophilic substitution of hydrogen (ONSH) derived compounds. After optimization, this reaction allowed easy access to interesting 3-nitro-substituted N,N′-dipyridinylamines. Georg Thieme Verlag Stuttgart.
- Patriciu, Oana-Irina,Pillard, Christelle,Finaru, Adriana-Luminita,Sandulescu, Ioan,Guillaumet, Gerald
-
p. 3868 - 3876
(2008/09/17)
-
- Highly efficient and practical phosphoramidite-copper catalysts for amination of aryl iodides and heteroaryl bromides with alkylamines and N(H)-heterocycles
-
A highly efficient copper-catalyzed system using phosphoramidite as ligands was applied to N-arylation of alkylamines and N(H)-heterocycles with aryl iodides and heteroaryl bromides. The reactions were carried out in relative mild conditions and good to excellent yields were obtained.
- Zhang, Zhanjin,Mao, Jincheng,Zhu, Di,Wu, Fan,Chen, Huilin,Wan, Boshun
-
p. 4435 - 4443
(2007/10/03)
-
- Identification of novel PPARα ligands by the structural modification of a PPARγ ligand
-
To develop novel PPARα ligands, we designed and synthesized several 3-{3-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives. Compound 10, the meta isomer of a PPARγ agonist 1, has been identified as a PPARα ligand. The introduction of methyl and ethyl groups at the C-2 position of the propanoic acid of 10 further improved the PPARα-binding potency.
- Usui, Shinya,Fujieda, Hiroki,Suzuki, Takayoshi,Yoshida, Naoaki,Nakagawa, Hidehiko,Miyata, Naoki
-
p. 3249 - 3254
(2007/10/03)
-
- Design, synthesis, and biological activity of novel PPARγ ligands based on rosiglitazone and 15d-PGJ2
-
To develop novel PPARγ ligands, we synthesized thirteen 3-{4-(2-aminoethoxy)phenyl}propanoic acid derivatives, which are designed based on the structures of rosiglitazone and 15d-PGJ2. Among these compounds, compound 9 was found to be as potent as rosiglitazone in a binding assay and a preadipocyte differentiation test. Molecular modeling suggested that the nonyl group of 9 interacted with hydrophobic amino acid residues constructing the hydrophobic region of PPARγ protein where the alkyl chain of 15d-PGJ2 is expected to be located.
- Usui, Shinya,Suzuki, Takayoshi,Hattori, Yoshifumi,Etoh, Kazuma,Fujieda, Hiroki,Nishizuka, Makoto,Imagawa, Masayoshi,Nakagawa, Hidehiko,Kohda, Kohfuku,Miyata, Naoki
-
p. 1547 - 1551
(2007/10/03)
-
- Synthesis of Secondary Arylamines through Copper-Mediated Intermolecular Aryl Amination
-
(Equation presented) A mild intermolecular copper-mediated amination of aryl iodides has been developed. The reaction takes place at room temperature or heating at 90°C and tolerates halogens attached to the aromatic ring. Its synthetic applications include a synthetic protocol for unsymmetrical N,N′-dialkylated phenylenediamines and both a stepwise and a general synthetic method for N-aryl secondary amines via Ns-anilides (readily obtained by reaction of the Ns-amide).
- Okano, Kentaro,Tokuyama, Hidetoshi,Fukuyama, Tohru
-
p. 4987 - 4990
(2007/10/03)
-
- Pyridinium N-,(2'-azinyl)aminides: Regioselective synthesis of 2- alkylaminoazines
-
The regioselective alkylation of pyridinium-N-(2f'-azinil)aminides with alkyl halides under mild conditions is described. The alkylation, combined with a reduction of the N-N bond, allows an easy preparation of 2- alkylaminoazines. (C) 2000 Elsevier Science Ltd.
- Martínez-Barrasa, Valentín,Delgado, Francisca,Burgos, Carolina,Luis García-Navío,Luisa Izquierdo,Alvarez-Builla, Julio
-
p. 2481 - 2490
(2007/10/03)
-
- Ruthenium complex-controlled catalytic N-mono- or N,N-dialkylation of heteroaromatic amines with alcohols
-
Heteroaromatic amines were N-alkylated with primary alcohols at 150-200°C in the presence of a catalytic amount of various ruthenium complexes to give the corresponding monoalkylated and dialkylated amines in good to high yields. For example, 2-aminopyridine reacted with an excess of ethanol at 180°C for 20 h in the presence of dichlorotris(triphenylphosphine)ruthenium [RuCl2-(PPh3)3] to give 2-(ethylamino)pyridine (1) and 2-(diethylamino)pyridine (2) in 9% and 70% yields, respectively. On the other hand, when (η4-1,5-cyclooctadiene)(η 6-1,3,5-cyclooctatriene)ruthenium [Ru(cod)(cot)] was used as a catalyst, even in the presence of excess ethanol, 1 was obtained in 85% yield with high selectivity. The addition of tertiary phosphines and phosphites to Ru(cod)-(cot) increased the yield of the dialkylated amine.
- Watanabe, Yoshihisa,Morisaki, Yasuhiro,Kondo, Teruyuki,Mitsudo, Take-Aki
-
p. 4214 - 4218
(2007/10/03)
-
- Regioselective Alkylation of the Exocyclic Nitrogen of Heterocyclic Amidines via the Mitsunobu Reaction
-
Regioselective alkylation of heterocyclic amidines by means of Mitsunobu reaction leads to L-aminoacid derivatives.
- Abarghaz, Mustapha,Kerbal, Abdelali,Bourguignon, Jean-Jacques
-
p. 6463 - 6466
(2007/10/02)
-
- AMINOLYSIS OF HALOGENOPYRIDINES AT HIGH PRESSURES
-
The transformation of some halogenopyridines to the corresponding aminopyridines has been realized in moderate to excellent yields at high pressures of 6 to 8 kbar.
- Hashimoto, Shiro,Otani, Shinichi,Okamoto, Tadashi,Matsumoto, Kiyoshi
-
p. 319 - 322
(2007/10/02)
-