- Mechanistic insights into the Pd(BINAP)-catalyzed amination of aryl bromides: Kinetic studies under synthetically relevant conditions
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Kinetic studies using reaction calorimetry were carried out under synthetically relevant conditions to study the mechanism of the amination of bromobenzene with primary and secondary amines using Pd2(dba)3/BINAP mixtures as well as p
- Singh, Utpal K.,Strieter, Eric R.,Blackmond, Donna G.,Buchwald, Stephen L.
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- Dimenthylphosphine P-Oxide as a Synthetic Platform for Bulky and Chiral Ligands with Dimenthylphosphino Donor Groups
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Attaching di(1R)-menthylphosphino fragments (menthyl = Men = 1R,2S,5R-2-isopropyl-5-methylcyclohex-1-yl) to molecular scaffolds turns them into homochiral, bulky, electron-rich phosphine ligands with proven and potential applications in coordination chemistry and transition-metal catalysis. Dimenthylphosphine P-oxide (Men2POH; 1) is established as a platform chemical toward dimenthylphosphino-containing targets via transformation to the known ligand precursors dimenthylchlorophosphine (4) and dimenthylphosphine (6). Transformations of 1 to dimenthylphosphinyl chloride (5) and dimenthylphosphinic acid (8) are elaborated. A phospha-Michael type 1,4-addition of 1 to p-benzo-or 1,4-naphthoquinone gives the corresponding o-hydroxyaryl(dimenthyl)phosphine oxides. Deprotonation of 1 with n-BuLi provides a phosphinyl nucleophile, whose reactions with alkyl halides or 1,n-dihaloalkanes provide tertiary alkyl dimenthylphosphine oxides or 1,n-bis(dimenthylphosphino)alkane bis(P-oxides) 10a-c, respectively. As an example, oxide 10b was deoxygenated to the diphosphine Men2P(CH2)3PMen2 (11) and characterized via the square-planar complex [(Men2P(CH2)3PMen2)PdCl2] (12). A selection of P-aryl dimenthylphosphines, including PhP(Men)2 (19) and 2-ClC6H4P(Men)2 (22), as well as the menthyl analogues Men-JohnPhos (21) and Men-SPhos (24), of the respective Buchwald ligands have been prepared. The combination of the secondary phosphine oxide (SPO) 1 with PdCl2 produces halide-bridged [(Men2POH)2Pd2Cl2] (25), mononuclear [(Men2POH)2PdCl2] (26), or the halide-bridged pseudochelate complex [(Men2PO···H···OPMen2)2Pd2Cl2] (27), depending on the reaction stoichiometry and conditions, all of which have been crystallographically characterized. The new ligands 1, 19, 21, 22, and 24 and complexes 25 and 26 have been evaluated in model palladium-catalyzed C-C-and C-N-fragment coupling reactions and found to display specific reactivity profiles due to the presence of the menthyl groups. Ligand 22 in particular catalyzed an asymmetric biaryl-forming coupling to give 2-methoxy-1,1′-binaphthalene with an er of up to 93:7.
- Reinhardt, Katja,Koller, Sebastian,Klein, Philippe,Lossin, Corvin,Gatzka, Julia,Altmann, Philipp J.,P?thig, Alexander,Hintermann, Lukas
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- Mechanistic study of nucleophilic fluorination for the synthesis of fluorine-18 labeled fluoroform with high molar activity fromN-difluoromethyltriazolium triflate
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The synthesis of fluorine-18 labeled fluoroform with high molar activity has grown in importance for the development of fluorine-18 labeled aryl-CF3radiopharmaceuticals that are useful as diagnostic radiotracers for the powerful technique of positron emission tomography (PET). We designed a strategy of synthesizing fluorine-18 labeled fluoroform fromN1-difluoromethyl-N3-methyltriazolium triflate (1)viaSN2 fluorination without stable fluorine isotope scrambling. Fluoroform was generated at rt in 10 min by fluorination of the triazolium precursor with TBAF (6 equiv.). We propose three routes (a), (b), and (c) for this fluorination. Quantum chemical calculations have been carried out to elucidate the mechanism of experimentally observed nucleophilic attack of fluoride at difluoromethyl groupviaroute (a), notN3-methylviaroute (b).1H and19F NMR studies using deuterium source have been performed to examine the competition between SN2 fluorination (route (a)) and the formation of difluorocarbene (route (c)). The observed superiority of SN2 pathway to formation of difluorocarbene in the reaction of the precursor using CsF in (CD3CN/(CD3)3COD (17.8?:?1)) gives the possibility of preparing the fluorine-18 labeled fluoroform in high molar activity.
- Chai, Jin Young,Cha, Hyojin,Lee, Sung-Sik,Oh, Young-Ho,Lee, Sungyul,Chi, Dae Yoon
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p. 6099 - 6106
(2021/02/12)
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- New Insights into the Reaction Capabilities of Ionic Organic Bases in Cu-Catalyzed Amination
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The application of ionic organic bases in the copper-catalyzed amination reaction (Ullmann reaction) has been studied at room temperature, with sub-mol-% catalyst loadings, and with more challenging amines at elevated temperatures. The cation present in the base has been shown to have little effect on the reaction at standard catalyst and ancillary ligand loadings, whereas the choice of anion is crucial for good reactivity. A substrate scope carried out at room temperature with the best performing bases, TBAM and TBPM, showed both bases to be highly effective under these mild reaction conditions. Moreover, under sub-mol % catalyst loadings and room temperature conditions, TBPM gave good to excellent yields for a number of different amines and functionalized aryl iodides (14 examples). However, reactions involving more challenging amines gave little or no yield. By using more forceful conditions (120 °C) moderate to excellent yields of cross-coupled products containing more challenging amines was achievable using TBPM and to a lesser extent with TBAM. As part of this work a study on the stability of the organic bases at 120 °C was undertaken. TBAM is shown to decompose to give nBu3N and mono-butylmalonate at higher temperatures, and this can be correlated to a decrease in performance in the coupling reaction. The phosphonium cations in TBPM did not undergo analogous reactivity but were shown instead to experience some degree of deprotonation at the α-CH2 to generate phosphonium ylides. This however did not lead to a significantly degradation in the activity of the TBPM in the cross-coupling reaction.
- Lo, Quintin A.,Sale, David,Braddock, D. Christopher,Davies, Robert P.
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p. 1944 - 1951
(2019/02/19)
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- 1,4-Dioxane-Tuned Catalyst-Free Methylation of Amines by CO2 and NaBH4
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A catalyst-free reductive functionalization of CO2 with amines and NaBH4 was developed. The N-methylation of amines was carried out with CO2 as a C1 building block and 1,4-dioxane as the solvent. Notably, the six-electron reduction of CO2 to form the methyl group occurred simultaneously with formation of the C?N bond to give the N-methylated amine.
- Guo, Zhiqiang,Zhang, Bo,Wei, Xuehong,Xi, Chanjuan
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p. 2296 - 2299
(2018/07/31)
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- Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach
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A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Kn?lker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono- or dimethylation in excellent isolated yields (>60 examples, 79% average yield).
- Polidano, Kurt,Allen, Benjamin D. W.,Williams, Jonathan M. J.,Morrill, Louis C.
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p. 6440 - 6445
(2018/07/25)
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- n-Butyllithium-mediated synthesis of N-aryl tertiary amines by reactions of fluoroarenes with secondary amines at room temperature
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A simple and facile method for the synthesis of aromatic tertiary amines by amination of fluoroarenes with secondary amines in the presence of n-butyllithium at room temperature was reported.
- Lin, Yingyin,Li, Meng,Ji, Xinfei,Wu, Jingjing,Cao, Song
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p. 1466 - 1472
(2017/02/18)
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- Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions
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NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.
- Nguyen, Thanh V. Q.,Yoo, Woo-Jin,Kobayashi, Shu
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supporting information
p. 452 - 458
(2016/02/12)
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- C–N cross-coupling on supported copper catalysts: The effect of the support, oxidation state, base and solvent
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A series of supported copper catalysts at two different loadings (1 and 2?wt%) have been prepared by deposition precipitation on various supports including TiO2, ZnO, Al2O3 and active carbon and submitted or not to reductive treatments to favor the increase in population of Cu(I). The samples have been characterized by textural measurements, electron microscopy and spectroscopic techniques including EPR and XPS, concluding the presence of dispersed copper oxides on the support with small particle size and contrasting prevalence of Cu(II) or Cu(I). The catalytic activity of all these catalysts for the C–N coupling of aniline and bromobenzene has been evaluated. A strong influence of the support, copper oxidation state, solvent, nature of the base was observed, the optimal conditions being the use of ZnO or TiO2 as supports and toluene/dioxane as solvent and EtOK as base. t-C5H11OK as base in either THF or toluene give rise to the formation of t-C5H11 phenyl ether in some extent. The catalyst undergoes deactivation during the reaction, but about 88% of the activity of the fresh sample could be regained by dioxane washings before reuse. XPS indicates that the most likely origin of catalyst deactivation is adsorption on the copper catalyst surface of KBr and inorganic salts formed as byproducts during the reaction.
- Tirsoaga, Alina,Cojocaru, Bogdan,Teodorescu, Cristian,Vasiliu, Florin,Grecu, Maria Nicoleta,Ghica, Daniela,Parvulescu, Vasile I.,Garcia, Hermenegildo
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p. 205 - 220
(2016/08/04)
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- Palladium-catalyzed amination of aryl sulfides with aliphatic amines
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Conditions for the palladium-NHC-catalyzed amination of aryl sulfides with aliphatic as well as aromatic amines were established. The KHMDS-mediated amination of heteroaryl sulfides could proceed without palladium. Based on the distinct difference in reactivity of C-Br and C-S bonds, a sequential amination of bromothioanisole can take place to install two different alkylamino groups onto the aromatic ring in one pot. A palladium-NHC precatalyst shows high efficiency for C-S bond cleavage for the amination of aryl sulfides with aliphatic amines or aromatic amines.
- Gao, Ke,Yorimitsu, Hideki,Osuka, Atsuhiro
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supporting information
p. 2678 - 2682
(2015/04/27)
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- Ligand-free C-C and C-N cross-couplings with Pd/Nf-G nanocomposite
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Abstract The catalytic activity of electrochemical deposited Pd nanoparticles on nafion-graphene support was examined for Buchwald-Hartwig amination reaction and Heck coupling reaction. The developed protocol is very efficient and ecofriendly, providing excellent product yield. The Pd/Nf-G catalyst can be used up to four cycles with slight decrease in catalytic activity.
- Shelkar, Radheshyam S.,Shendage, Suresh S.,Nagarkar, Jayashree M.
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supporting information
p. 4463 - 4467
(2015/06/30)
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- Coupling of boronic acids with amines in the presence of a supported copper catalyst
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An efficient heterogeneous catalytic method was developed for Chan-Lam reaction, coupling of amines and boronic acid. Copper on 4 A molecular sieve provided yields comparable to the methods published. The method provides the main advantages of a heterogeneous catalytic procedure, the preparation of the catalyst is easy, the workup of the reaction mixture is simple. Graphical abstract: [Figure not available: see fulltext.]
- Debreczeni, Nora,Fodor, Anna,Hell, Zoltan
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p. 1547 - 1551,5
(2014/11/12)
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- Nano Pd-Fe3O4@Alg beads: As an efficient and magnetically separable catalyst for Suzuki, Heck and Buchwald-Hartwig coupling reactions
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Catalytic processes are the backbone of many chemical industries. In a comparative study of various heterogeneous catalytic systems, we report efficient and magnetically separable nano Pd-Fe3O4@Alg beads as catalysts for Suzuki, Heck and Buchwald-Hartwig coupling reactions. This catalyst was characterized by SEM, TEM, HRTEM, XRD, EDAX, FT-IR, VSM, DSC-TGA, BET, and UV-Visible spectroscopy. This heterogeneous catalyst showed high catalytic activity and stability for C-C and C-N bond forming coupling reactions with excellent product yield under ligand free conditions. The beads of nano Pd-Fe3O4@Alg can be separated from the reaction mixture by an external magnet and reused for several successive cycles with no appreciable loss in the catalytic activity. The Suzuki and Heck coupling reactions in aqueous medium are greener routes, which is an added advantage of this protocol. This journal is
- Shelkar, Radheshyam S.,Gund, Sitaram H.,Nagarkar, Jayashree M.
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p. 53387 - 53396
(2015/02/05)
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- The facet-dependent enhanced catalytic activity of Pd nanocrystals
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A systematic study of heterogeneous Buchwald-Hartwig amination using shape-controlled Pd nanocrystals with distinctly different surface facets is presented. This journal is the Partner Organisations 2014.
- Kim, Minjune,Kim, Yeonjoon,Hong, Jong Wook,Ahn, Seihwan,Kim, Woo Youn,Han, Sang Woo
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supporting information
p. 9454 - 9457
(2014/08/18)
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- Microwave-assisted amination from fluorobenzenes without catalyst and strong base
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A facile and versatile amination of fluorobenzenes has been developed in good to excellent yields under microwave irradiation in N-methylpyrrolidinone (NMP) without strong base and catalyst. The presence of additional halogen atom(s) enhanced the leaving ability of fluorine and meta fluorine gave higher activation than the ortho. It is remarkable that 1,2,3-trifluorobenzene, 1,2,4-trifluorobenzene and 1,2,4,5-tetrafluorobenzene can produce the regioselective mono-substituted products.
- Meng, Xiangguo,Cai, Zhengyan,Xiao, Sa,Zhou, Weicheng
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- Sulfur, oxygen, and nitrogen mustards: Stability and reactivity
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Mustard gas, bis(β-chloroethyl) sulfide (HD), is highly toxic and harmful to humans and the environment. It comprises one class of chemical warfare agents (CWAs) that was used in both World Wars I and II. The three basic analogues or surrogates are: the monochloro derivative, known as the half mustard, 2-chloroethyl ethyl sulfide (CEES); an oxygen analogue, bis(β-chloroethyl) ether (BCEE); and several nitrogen analogues based on the 2,2′-dichlorodiethylamine framework (e.g., HN1, HN2, and HN3). The origin of their toxicity is considered to be from the formation of three-membered heterocyclic ions, a reaction that is especially accelerated in aqueous solution. The reaction of these cyclic ion intermediates with a number of important biological species such as DNA, RNA and proteins causes cell toxicity and is responsible for the deleterious effects of the mustards. While a number of studies have been performed over the last century to determine the chemistry of these compounds, early studies suffered from a lack of more sophisticated NMR and X-ray techniques. It is now well-established that the sulfur and nitrogen mustards are highly reactive in water, while the oxygen analog is much more stable. In this study, we review and summarize results from previous studies, and add results of our own studies of the reactivity of these mustards toward various nonaqueous solvents and nucleophiles. In this manner a more comprehensive evaluation of the stability and reactivity of these related mustard compounds is achieved.
- Wang, Qi-Qiang,Begum, Rowshan Ara,Day, Victor W.,Bowman-James, Kristin
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p. 8786 - 8793
(2013/01/15)
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- Efficient catalytic aryl amination of bromoarenes using 3-iminophosphine palladium(II) chloride
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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.
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p. 7 - 18,12
(2012/12/12)
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- A highly efficient precatalyst for amination of aryl chlorides: Synthesis, structure and application of a robust acenaphthoimidazolylidene palladium complex
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A robust palladium NHC complex was synthesized and exhibits exceptional activity and selectivity as a precatalyst in the amination of aryl chlorides and tolerates a wide range of substrates at low catalyst loadings.
- Tu, Tao,Fang, Weiwei,Jiang, Jian
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supporting information; experimental part
p. 12358 - 12360
(2011/12/15)
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- Examination of the aromatic amination catalyzed by palladium on charcoal
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The Buchwald-Hartwig amination of aryl halides with secondary amines and functionalized aromatic amines catalyzed by solid-supported palladium is reported. The choices of ligand, base and solvent are crucial for the successful coupling. The ami-nation of aromatic iodides, bromides and chlorides can be easily achieved with palladium on charcoal in the presence of a biphenylphosphane-type ligand at 80-110 °C. In addition, the palladium on charcoal catalyst is easily separable after the reaction, and reusable several times with only small activity loss.
- Komaromi, Anna,Novak, Zoltan
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supporting information; experimental part
p. 1523 - 1532
(2010/08/19)
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- A highly versatile catalyst system for the cross-coupling of aryl chlorides and Amines
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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
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supporting information; experimental part
p. 1983 - 1991
(2010/07/03)
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- Transition metal-free amination of aryl halides-A simple and reliable method for the efficient and high-yielding synthesis of N-arylated amines
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A simple and reliable reaction protocol for the clean, fast, and high-yielding synthesis of various N-arylated amines derived from reactions of aryl halides with various (also sterically hindered) amines under transition metal-free reaction conditions is presented. Dioxane and KN(Si(CH3)3)2 were found to be the ideal solvent and base for this transformation. The conversion rates and yields observed are excellent and in the majority of the reactions performed significantly higher than that obtained in their catalyzed versions. Furthermore, the selective synthesis of 6-halopyridin-2-amines and asymmetric pyridine-2,6-diamines (derived from consecutive reactions of 2,6-dibromopyridine and 2,6-dichloropyridine, respectively, with different amines) is possible in almost quantitative yields (relative to 2,6-dihalopyridine) within very short reaction times. Purification of the 6-halopyridin-2-amine intermediates is not necessary, allowing the synthesis of pyridine-2,6-diamines in 'one-pot'. However, catalysts are in many cases not required to efficiently and selectively couple aryl halides with amines, making transition metal-free versions of the Buchwald-Hartwig reaction extremely attractive for the synthesis of N-arylated amines with substrates containing substituents on the aryl halide, which either promote regioselectivity and/or do not require regioselective aminations.
- Bolliger, Jeanne L.,Frech, Christian M.
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experimental part
p. 1180 - 1187
(2009/04/10)
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- Synthesis and use of MSE-framework type molecular sieves
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A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, tita
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Page/Page column 5-6
(2009/12/28)
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- Benzofurans as suppressors of neurodegeneration
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A compound of the formula: wherein R1 and R2 each is H or a hydrocarbon group which may be substituted, or R1 and R2 form a 3- to 8-membered carbo or heterocyclic ring which may be substituted; R3 is H, a lower alkyl which may be substituted or an aromatic group which may be substituted; R4 is (1) an aromatic group which may be substituted, (2) an aliphatic hydrocarbon group substituted by an aromatic group which may be substituted, which hydrocarbon group may be further substituted or (3) an acyl; X and Y each is oxygen or sulfur which may be oxidized; and ring A is a benzene ring which may be further substituted, or a salt thereof, is useful for an agent for suppressing neurodegeneration.
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Page/Page column 37
(2010/10/20)
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- Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives
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A series of substituted piperazine derivatives have been synthesized and tested for antimicrobial activity. The antibacterial activity was tested against Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652), and antifungal activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. All synthesized compounds showed significant activity against bacterial strains but were found to be less active against tested fungi. In vitro toxicity tests demonstrated that compounds 4d and 6a showed very less toxicity against human erythrocytes.
- Chaudhary, Preeti,Kumar, Rupesh,Verma, Akhilesh K.,Singh, Devender,Yadav, Vibha,Chhillar, Anil K.,Sharma,Chandra, Ramesh
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p. 1819 - 1826
(2007/10/03)
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- Highly efficient and practical phosphoramidite-copper catalysts for amination of aryl iodides and heteroaryl bromides with alkylamines and N(H)-heterocycles
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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
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p. 4435 - 4443
(2007/10/03)
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- Aromatic amination of aryl bromides catalysed by copper/β-diketone catalysts: The effect of concentration
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CuCl ligated with β-diketones were found to be good catalysts for the animation of aryl bromides. Crucial is the concentration of the substrates: at 5 M the rate and selectivity improves substantially. In addition, K 2CO3 can be used as base instead of expensive Cs 2CO3. Primary and secondary amines, heterocycles and anilines could be arylated in good yields. Georg Thieme Verlag Stuttgart.
- De Lange, Ben,Lambers-Verstappen, Marielle H.,Schmieder-Van De Vondervoort, Lizette,Sereinig, Natascha,De Rijk, Ron,De Vries, André H. M.,De Vries, Johannes G.
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p. 3105 - 3109
(2008/02/13)
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- Gram-scale synthesis of N-aryl- and N-aryl-N′-methylpiperazines on a novel, water-swellable, oxethane-linked poly(ethylene glycol) high-loading resin
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A new methodology for the synthesis of N-arylpiperazines was developed using a poly(ethylene glycol)-derived solid support. The reactions proceeded in up to 60% overall yield over four steps. The scope and limitations of the method are discussed, as well as the utility of 13C gel-phase NMR spectroscopy for reaction monitoring. Georg Thieme Verlag Stuttgart.
- Rudbeck, Hans Christian,Johannsen, Ib,Nielsen, Ole,Ruhland, Thomas,Sommer, Michael Bech,Tanner, David,Dancer, Robert
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p. 3456 - 3462
(2007/10/03)
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- Microwave-assisted amination from aryl triflates without base and catalyst
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(Equation presented) Aryl triflates are effectively converted to the corresponding anilines under microwave irradiation in 1-methyl-2-pyridone (NMP) without base and catalyst. Aryl triflates substituted with both electron-poor and electron-rich groups give good to excellent yields. It is noteworthy that the halogenated aryl triflates can chemoselectively react with amines to afford halogenated anilines.
- Xu, Gang,Wang, Yan-Guang
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p. 985 - 987
(2007/10/03)
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- PROMOTERS FOR THE PROLIFERATION AND DIFFERENTIATION OF STEM CELLS AND/OR NEURON PRECURSOR CELLS
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An agent for promoting the proliferation or differentiation of a stem cell and/or neural progenitor cell, comprising a compound represented by Formula: wherein each of R1 and R2 is H, a hydrocarbon group or a heterocyclic group, or taken together with the adjacent carbon atom to form a ring, R3 is H, a hydrocarbon group or a heterocyclic group, W is a group represented by Formula: wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring, R4 is an acyl group having an aliphatic hydrocarbon group, which is substituted by an aromatic group and may have a further substitutent, or aromatic group, R5 is H, C1-6 alkyl or acyl, R4c is an aromatic group, an aliphatic hydrocarbon group or acyl, and X is O or S; Y is O, S or NH, Ring C is an optionally substituted benzene ring, or a salt or prodrug thereof is provided.
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- Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds
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The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of an amide or amine moiety and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In additional embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between a nitrogen atom of an acyl hydrazine and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In other embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of a nitrogen-containing heteroaromatic, e.g., indole, pyrazole, and indazole, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-oxygen bond between the oxygen atom of an alcohol and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. The present invention also relates to copper-catalyzed methods of forming a carbon-carbon bond between a reactant comprising a nucleophilic carbon atom, e.g., an enolate or malonate anion, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. Importantly, all the methods of the present invention are relatively inexpensive to practice due to the low cost of the copper comprised by the catalysts.
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- Nickel catalyzed cross-coupling and amination reactions of aryl nitriles
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Aryl nitriles have been found to participate in cross-coupling and amination reactions via nickel-catalyzed activation of the C-CN bond. With the development of these synthetically useful transformations, aryl nitriles can now be considered along with ary
- Miller, Joseph A.,Dankwardt, John W.,Penney, Jonathan M.
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p. 1643 - 1648
(2007/10/03)
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- Copper-catalyzed coupling of alkylamines and aryl iodides: an efficient system even in an air atmosphere.
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[reaction: see text] A mild method for the copper-catalyzed amination of aryl iodides is reported. This operationally simple C-N bond-forming protocol uses CuI as the catalyst and ethylene glycol as ligand in 2-propanol. A variety of functionalized aryl iodides as well as several amines were efficiently coupled using this method. This catalytic amination procedure is relatively insensitive to moisture and can be performed under an air atmosphere with comparable yield. Preliminary results on the amination of aryl bromides are also described.
- Kwong, Fuk Yee,Klapars, Artis,Buchwald, Stephen L
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p. 581 - 584
(2007/10/03)
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- Nickel-catalysed amination of aryl chlorides using a dihydroimidazoline carbene ligand
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A new arylamination protocol has been developed using a catalyst combination prepared from Ni(acac)2 associated to a sterically hindered dihydroimidazoline carbene ligand. A high efficiency was attained using, in most cases, only 2 mol% Ni/carbene clusters.
- Gradel, Benot,Brenner, Eric,Schneider, Rapha?l,Fort, Yves
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p. 5689 - 5692
(2007/10/03)
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- Soluble polymer bound cleavage reagents: A multipolymer strategy for the cleavage of tertiary amines from REM resin
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(equation presented) Soluble polymer bound reagent 1 has been prepared to cleave tertiary amines from REM resin. Normally, amines cleaved from REM resin require extraction or chromatography to remove excess cleavage reagent and its byproducts. The solubility profile of non-crosslinked polystyrene (NCPS) based reagent 1 eliminates the need for such purification and allows for the direct isolation of a library of pure tertiary amines through simple filtration and concentration operations.
- Toy, Patrick H.,Reger, Thomas S.,Janda, Kim D.
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p. 2205 - 2207
(2007/10/03)
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- Hybridized and isosteric analogues of N1-acetyl-N4-dimethyl-piperazinium iodide (ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (DMPP) with central nicotinic action
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A series of piperazine derivatives, obtained by hybridization of N1-acetyl-N4-dimethyl-piperazinium iodide (1, ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (3, DMPP) or of the corresponding tertiary bases (2, 4) with arecoline (5) and arecolone (6) or by isosteric substitution of the phenyl ring of DMPP, has been synthesized. Hybridization afforded compounds that, both as tertiary bases and as iodomethylates, have no affinity for the nicotinic receptor. On the contrary, isosteric substitution gave compounds that maintain affinity for the receptor; among them, two tertiary bases (37, 38), show affinity in the nanomolar range for the nicotinic receptor. The pharmacological profile of these isomeric compounds is quite interesting as they present differences in their peripheral and central effects, suggesting that they interact with different subtypes of the nicotinic receptor. Copyright (C) 1999 Elsevier Science Ltd.
- Manetti, Dina,Bartolini, Alessandro,Borea, Pier Andrea,Bellucci, Cristina,Dei, Silvia,Ghelardini, Carla,Gualtieri, Fulvio,Romanelli, Maria Novella,Scapecchi, Serena,Teodori, Elisabetta,Varani, Katia
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p. 457 - 465
(2007/10/03)
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- Nickel-catalysed couplings of aryl chlorides with secondary amines and piperazines
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The reaction of aryl chlorides with secondary amines or piperazines in the presence of an in situ generated liganded nickel catalyst gives arylamines in good yields. Our process provides a mild, convenient and cheap method of arylamination starting from readily available substrates.
- Brenner, Eric,Schneider, Raphael,Fort, Yves
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p. 12829 - 12842
(2007/10/03)
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- Ruthenium-complex-catalyzed N-(Cyclo)alkylation of aromatic amines with diols. Selective synthesis of N-(ω-hydroxyalkyl)anilines of type PhNH(CH2)(n)OH and of some bioactive arylpiperazines
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A new class of well-defined neutral mono-, and dicationic ruthenium(II) complexes containing a neutral terdentate donor system [C5H3N(CH2E)2- 2,6] (E = PPh2 (PNP) or NME2 (NN'N) has been found effective as catalyst precursor in N-(cyclo)alkylation reactions of aromatic amines with diols Y(CH2CH2OH)2 (Y = CH2, NR). With these catalysts, N-phenylpiperidine is synthesized from aniline and 1,5-pentanediol in 85% yield (at 180 °C for 24 h in 1.4-dioxane). With neutral RuCl2(NN'N)-(PPh3) as a catalyst precursor, aniline can be selectively N-monoalkylated with diols of the type HO(CH2)(n)OH (n = 4-6, 10) to give N-(n-hydroxyalkyl)anilines in 40-75 yield. To our knowledge, this represents the first useful catalytic route to this type of compounds. The new catalysts can also be used in the synthesis of arylpiperazines. For example, N-phenyl-N'-methylpiperazine is obtained from aniline and MeN(CH2CH2OH)2 in yields up to 34%. N- [m(Trifluoromethyl)phenyl]-N'-methylpiperazine, TFMPMP, is successfully produced from m-(trifluoromethyl)aniline and MeN-(CH2CH2OH)2 in 44% yield using monocationic [RuOTf(NN'N)(PPh3)]OTf as the catalyst precursor. A mechanism for the N-(cyclo)alkylation reaction is proposed.
- Abbenhuis,Boersma,Van Koten
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p. 4282 - 4290
(2007/10/03)
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- Carbamate linkers as latent N-methylamines in solid phase synthesis
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A new linker strategy for solid phase synthesis has been developed. It utilizes LAH reduction of a carbamate connection to Wang resin which results in N-methylamines, a useful functionality in medicinal chemistry.
- Ho, Chih Y.,Kukla, Michael J.
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p. 2799 - 2802
(2007/10/03)
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- Palladium-catalyzed amination of aryl chlorides
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Pd(PCy3)Cl2 (Cy = cyclohexyl) catalyzed the reaction of aryl chlorides and secondary amines in the presence of NaO(t)Bu to give the corresponding aryl amines in good to excellent yields. In some of the reactions, an excess amount of aryl chloride (aryl chloride/amine = 2) improved the yields.
- Reddy, Nagavelli Prabhakar,Tanaka, Masato
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p. 4807 - 4810
(2007/10/03)
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- Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
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Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH3CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)3 gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH4.
- Abdel-Magid, Ahmed F.,Carson, Kenneth G.,Harris, Bruce D.,Maryanoff, Cynthia A.,Shah, Rekha D.
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p. 3849 - 3862
(2007/10/03)
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- Synthesis of arylpiperazines via nucleophilic aromatic substitution of (η6-fluoroarene)tricarbonylchromium complexes
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A one-pot, high yield preparation procedure for the synthesis of arylpiperazines using a nucleophilic aromatic substitution of (η6-fluoroarene)tricarbonylchromium complexes (including those bearing electron donating groups) is described. A new, easy and fast decomplexation procedure, in DMSO as solvent, is also presented.
- Perez, Michel,Potier, Pierre,Halazy, Serge
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p. 8487 - 8488
(2007/10/03)
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- Direct Substitution of Aromatic Ethers by Lithium Amides. A New Aromatic Amination Reaction
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Reaction of lithiated dialkylamines with methoxy aromatics in refluxing THF leads to products resulting from a direct ipso-substitution.Especially with lithiated secondary amines high conversions and selectivities are achieved.Sulfonyl-substituted aromatics react equally well, but halogenated aromatics give rise to side-products arising from a competing pathway via aryne intermediates.The scope and mechanistic implications of this novel nucleophilic amination reaction are described.
- Hoeve, Wolter ten,Kruse, Chris, G.,Luteyn, Jan M.,Thiecke, Janet R. G.,Wynberg, Hans
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p. 5101 - 5106
(2007/10/02)
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- Ruthenium Complex Catalyzed N-Heterocyclization. Syntheses of N-Substituted Piperidines, Morpholines, and Piperazines from Amines and 1,5-Diols
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1,5-Pentanediol reacts with aliphatic and aromatic primary amines in the presence of a ruthenium catalyst modified with phosphonic ligands to give N-substituted piperidines in fair to goods yields.The reactions were carried out at 150-180 deg C for 5 h in dioxane.The nature of the phosphorus ligands has a remarkable effect on the catalytic activity, For the reaction of aromatic amines, triphenylphosphine is effective, while for aliphatic amine more basic tributyl- or triethylphosphine is preferable.Amines also react with diethylene glycol and N-substituted diethanolamines in the presence of the ruthenium catalyst to give N-substituted morpholines and piperazines in good yields, respectively.
- Tsuji, Yasushi,Huh, Keun-Tae,Ohsugi, Yukihiro,Watanabe, Yoshihisa
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p. 1365 - 1370
(2007/10/02)
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- Photoinduced Electron Transfer in Polychromophoric Systems. 2. Protonation Directed Switching between Tri- and Bichromophoric Interaction.
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The synthesis of a series of molecules D2-D1-A is described in which two electron donor chromophores (D1, a trialkylamino group, and D2, a (substituted) anilino group) and an electron acceptor chromophore (A, a
- Mes, Ger F.,Ramesdonk, Hendrik J. van,Verhoeven, Jan W.
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p. 1335 - 1340
(2007/10/02)
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