- Continuous Synthesis of Aryl Amines from Phenols Utilizing Integrated Packed-Bed Flow Systems
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Aryl amines are important pharmaceutical intermediates among other numerous applications. Herein, an environmentally benign route and novel approach to aryl amine synthesis using dehydrative amination of phenols with amines and styrene under continuous-flow conditions was developed. Inexpensive and readily available phenols were efficiently converted into the corresponding aryl amines, with small amounts of easily removable co-products (i.e., H2O and alkanes), in multistep continuous-flow reactors in the presence of heterogeneous Pd catalysts. The high product selectivity and functional-group tolerance of this method allowed aryl amines with diverse functional groups to be selectively obtained in high yields over a continuous operation time of one week.
- Ichitsuka, Tomohiro,Kobayashi, Shū,Koumura, Nagatoshi,Sato, Kazuhiko,Takahashi, Ikko
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p. 15891 - 15896
(2020/07/13)
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- A General Palladium–Phosphine Complex To Explore Aryl Tosylates in the N-Arylation of Amines: Scope and Limitations
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The scope and limitations of the monoselective N-arylation of various amines by using aryl and hetaryl tosylates are presented. The air-stable and easily accessible Pd(OAc)2/CM-phos {CM-phos=2-[2-(dicyclohexylphosphino)phenyl]-1-methyl-1H-indole}catalyst system was able to deal with a wide range of aryl tosylate substrates as well as amine nucleophiles, including primary and secondary cyclic/acyclic aliphatic amines and anilines. NH-Bearing heterocycles such as indole, carbazole, pyrrole, 10-phenothiazine, and 10-phenoxazine were shown to be feasible coupling partners under this catalytic system. The described reaction conditions tolerate a wide range of functional groups and allow an array of aromatic amines as well as unsymmetrical amine products to be easily accessed from the various phenolic derivatives. Interestingly, this catalyst system even offers the opportunity to perform the reaction in water medium. We also report the intermolecular coupling of optically active α-central chiral amines with aryl tosylates without erosion of the enantiomeric purity.
- Choy, Pui Ying,Chung, Kin Ho,Yang, Qingjing,So, Chau Ming,Sun, Raymond Wai-Yin,Kwong, Fuk Yee
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supporting information
p. 2465 - 2474
(2018/09/10)
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- Synthesis of Di(hetero)arylamines from Nitrosoarenes and Boronic Acids: A General, Mild, and Transition-Metal-Free Coupling
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The synthesis of di(hetero)arylamines by a transition-metal-free cross-coupling between nitrosoarenes and boronic acids is reported. The procedure is experimentally simple, fast, mild, and scalable and has a wide functional group tolerance, including carbonyls, nitro, halogens, free OH and NH groups. It also permits the synthesis of sterically hindered compounds.
- Roscales, Silvia,Csák?, Aurelio G.
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p. 1667 - 1671
(2018/03/23)
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- Method for synthesis of 2-acetylphenothiazine from m-acetylchlorobenzene and benzamide
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The invention discloses a method for synthesis of 2-acetylphenothiazine from m-acetylchlorobenzene and benzamide. The method comprises that m-acetylchlorobenzene and benzamide undergo a Ullmann condensation reaction in a tert-butyl alcohol solvent in the presence of cuprous iodide and piperazine as catalysts, the reaction product undergoes a hydrolysis reaction in the presence of a strong base as a catalyst and the hydrolysis reaction product and a sulfur elementary substance undergo an annulation reaction in an acetone solvent in the presence of iodine as a catalyst. The 2-acetylphenothiazine is prepared from m-acetylchlorobenzene and benzamide as raw materials through a Ullmann condensation reaction, a hydrolysis reaction and an annulation reaction with the sulfur elementary substance. Benzamide is used as a nucleophilic reagent and P electrons on carbonyl carbon of benzamide produce electron donating conjugative effects so that electron cloud density of aryl nitrogen atoms is increased, nitrogen atom nucleophilicity is improved and a Ullmann condensation reaction rate is accelerated. The method guarantees a 2-acetylphenothiazine overall yield and purity through above two steps.
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Paragraph 0038; 0040
(2016/12/07)
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- Method for synthesis of 2-acetyl phenothiazine with m-acetyl phenol and aniline as raw materials
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The invention discloses to a method for synthesis of 2-acetyl phenothiazine with m-acetyl phenol and aniline as raw materials. The method comprises the steps: carrying out a dehydration reaction of m-acetyl phenol and aniline with trifluoromethanesulfonic acid as a catalyst; and carrying out an annulation reaction on the product obtained in the first step with elemental sulfur under the catalysis of iodine in an acetone solvent. With m-acetyl phenol and aniline as the raw materials, firstly, amino and phenolic hydroxyl are subjected to dehydration reaction, then the product is subjected to annulation reaction with elemental sulfur, and thus 2-acetyl phenothiazine is obtained. Trifluoromethanesulfonic acid as the dehydration reaction catalyst has stronger acidity and has the effect of relatively strongly protonizing m-acetyl phenol to form a molten salt, and the dehydration yield is increased. Through the two steps, the total yield and purity of 2-acetyl phenothiazine are ensured.
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Paragraph 0031; 0032
(2016/11/14)
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- Ligand-free C-N bond formation in aqueous medium using a reusable Cu-Mn bimetallic catalyst
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A general ligand-free protocol has been described for the recyclable and reusable Cu-Mn catalyzed C-N bond forming cross coupling reaction of arylboronic acids with various amines to form N-arylated amine products in aqueous medium affording excellent yields under ambient conditions, in 3-4 h.
- Sawant, Sanghapal D.,Srinivas, Mahesuni,Aravinda Kumar,Lakshma Reddy,Singh, Parvinder Pal,Singh, Baldev,Sharma, Amit Kumar,Sharma,Vishwakarma, Ram A.
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p. 5351 - 5354
(2013/09/12)
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- 9-Fluorenylphosphines for the Pd-catalyzed Sonogashira, Suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water
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The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl = Me. Et, /Pr, -Pr. -C18H25) in > 95% yields, for which lithiation and reaction with R2PCl (R = Cy, iPr, tBu) generates 9-alkyl, 9-PR2fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphinc complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira. Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120°C leads to >90% yields with 1 mol % of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol % of Pd catalyst at 100°C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol % of catalyst in pure water at 100°C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100°C by using 0.1-0.5 mol % of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in > 95 % yield.
- Fleckenstein, Christoph A.,Plenio, Herbert
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p. 2701 - 2716
(2008/03/14)
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- Expedited palladium-catalyzed amination of aryl nonaflates through the use of microwave-irradiation and soluble organic amine bases
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Microwave-assisted, palladium-catalyzed C-N bond-forming reactions with aryl/heteroaryl nonaflates and amines using the soluble amine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or MTBD (7-methyl-1,5,7-triazabicyclo[4.4. 0]dec-5-ene) and ligands (1-3) resulted in good to excellent yields (71-99%) of arylamines in short reaction times (1-45 min).
- Tundel, Rachel E.,Anderson, Kevin W.,Buchwald, Stephen L.
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p. 430 - 433
(2007/10/03)
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- Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi
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We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds that were effective against the enzymes and the parasites but also some compounds that were parasiticidal despite a lack of activity against the proteases. Several compounds were effective in killing all tested parasites. These promising lead compounds were tested for general toxicity in mice, and only one produced observable toxicity after 62 h. Our results suggest that thiosemicarbazones represent validated drug leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as other novel targets.
- Greenbaum, Doron C.,Mackey, Zachary,Hansell, Elizabeth,Doyle, Patricia,Gut, Jiri,Caffrey, Conor R.,Lehrman, Julia,Rosenthal, Philip J.,McKerrow, James H.,Chibale, Kelly
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p. 3212 - 3219
(2007/10/03)
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- Simple, efficient catalyst system for the palladium-catalyzed amination of aryl chlorides, bromides, and triflates
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Palladium complexes supported by (o-biphenyl)P(t-Bu)2 (3) or (o- biphenyl)PCy2 (4) are efficient catalysts for the catalytic amination of a wide variety of aryl halides and triflates. Use of ligand 3 allows for the room-temperature catalytic amination of many aryl chloride, bromide, and triflate substrates, while ligand 4 is effective for the amination of functionalized substrates or reactions of acyclic secondary amines. The catalysts perform well for a large number of different substrate combinations at 80-110 °C, including chloropyridines and functionalized aryl halides and triflates using 0.5-1.0 mol % Pd; some reactions proceed efficiently at low catalyst levels (0.05 mol % Pd). These ligands are effective for almost all substrate combinations that have been previously reported with various other ligands, and they represent the most generally effective catalyst system reported to date. Ligands 3 and 4 are air-stable, crystalline solids that are commercially available. Their effectiveness is believed to be due to a combination of steric and electronic properties that promote oxidative addition, Pd-N bond formation, and reductive elimination.
- Wolfe, John P.,Tomori, Hiroshi,Sadighi, Joseph P.,Yin, Jingjun,Buchwald, Stephen L.
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p. 1158 - 1174
(2007/10/03)
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