- Amination of Aryl halides and esters using intensified continuous flow processing
-
Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers.
- Kohl, Thomas M.,Hornung, Christian H.,Tsanaktsidis, John
-
-
Read Online
- Method for catalyzing N-alkylation of aminopyridine
-
The invention discloses a method for catalyzing N-alkylation of aminopyridine. The method comprises the step of reacting an aminopyridine compound with an alkylation raw material in the presence of a heterogeneous catalyst to obtain an N-alkylated aminopyridine compound. The alkylation reaction has high activity and selectivity, is simple to operate and low in catalyst price, does not need other reaction steps, is beneficial to large-scale industrial production, and compared with previous reports, does not need to use a large amount of noble metals, can be continuously carried out, and does not use other expensive organic raw materials or reducing agents in the process. Generation of a large amount of organic waste liquid and solid waste is avoided, and collection operation of process products is simple.
- -
-
Paragraph 0087-0091
(2021/08/07)
-
- 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
-
p. 1722 - 1729
(2021/04/19)
-
- CO2-tuned highly selective reduction of formamides to the corresponding methylamines
-
We herein describe an efficient, CO2-tuned and highly selective C-O bond cleavage of N-methylated formanilides. With easy-to-handle and commercially available NaBH4 as the reductant, a variety of formanilides could be turned into the desired tertiary amines in moderate to excellent yields. The role of CO2 has been investigated in detail, and the mechanism is proposed on the basis of experiments.
- Chao, Jianbin,Guo, Zhiqiang,Pang, Tengfei,Wei, Xuehong,Xi, Chanjuan,Yan, Leilei
-
supporting information
p. 7534 - 7538
(2021/10/12)
-
- 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
-
p. 10566 - 10576
(2019/12/02)
-
- N-Methylation of amines and nitroarenes with methanol using heterogeneous platinum catalysts
-
We report herein the selective N-methylation of amines and nitroarenes with methanol under basic conditions using carbon-supported Pt nanoparticles (Pt/C) as a heterogeneous catalyst. This method is widely applicable to four types of N-methylation reactions: (1) N,N-dimethylation of aliphatic amines under N2, (2) N-monomethylation of aliphatic amines under 40 bar H2, (3) N-monomethylation of aromatic amines under N2, and (4) tandem synthesis of N-methyl anilines from nitroarenes and methanol under 2 bar H2. All these reactions under the same catalytic system showed high yields of the corresponding methylamines for a wide range of substrates, high turnover number (TON), and good catalyst reusability. Mechanistic studies suggested that the reaction proceeded via a borrowing hydrogen methodology. Kinetic results combined with density functional theory (DFT) calculations revealed that the high performance of Pt/C was ascribed to the moderate metal–hydrogen bond strength of Pt.
- Jamil, Md.A.R.,Touchy, Abeda S.,Rashed, Md. Nurnobi,Ting, Kah Wei,Siddiki, S.M.A. Hakim,Toyao, Takashi,Maeno, Zen,Shimizu, Ken-ichi
-
-
- Expedient stereospecific Co-catalyzed tandem C-N and C-O bond formation of: N -methylanilines with styrene oxides
-
Cobalt(ii)-catalyzed stereospecific coupling of N-methylanilines with styrene oxides is developed via tandem C-N and C-O bond formation using tert-butyl hydroperoxide (TBHP) as an oxidant. Optically active epoxide can be reacted with high optical purity.
- Satheesh, Vanaparthi,Vivek Kumar, Sundaravel,Punniyamurthy, Tharmalingam
-
supporting information
p. 11813 - 11816
(2018/12/01)
-
- Efficient and versatile catalytic systems for the n-methylation of primary amines with methanol catalyzed by n-heterocyclic carbene complexes of iridium
-
Efficient and versatile catalytic systems were developed for the N-methylation of both aliphatic and aromatic primary amines using methanol as the methylating agent. Iridium complexes bearing an Nheterocyclic carbene (NHC) ligand exhibited high catalytic performance for this type of transformation. For aliphatic amines, selective N,N-dimethylation was achieved at low temperatures (50-90 °C). For aromatic amines, selective N-monomethylation and selective N,N-dimethylation were accomplished by simply changing the reaction conditions (presence or absence of a base with an appropriate catalyst). These findings can be used to develop methods for synthesizing useful amine compounds having N-methyl or N,N-dimethyl moieties.
- Toyooka, Genki,Tuji, Akiko,Fujita, Ken-Ichi
-
p. 4617 - 4626
(2019/02/01)
-
- Selective Monomethylation of Amines with Methanol as the C1 Source
-
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
- Choi, Geunho,Hong, Soon Hyeok
-
supporting information
p. 6166 - 6170
(2018/04/30)
-
- Efficient ruthenium-catalyzed N-methylation of amines using methanol
-
An in situ-generated complex from [RuCpCl2]2 and dpePhos ligand is reported as an efficient catalyst in the presence of 5 mol % of LiOtBu for the N-methylation of amines using methanol as the methylating agent at moderate conditions, following hydrogen borrowing strategy. This simple catalyst system provides selective N-monomethylation of substituted primary anilines and sulfonamides as well as N,N dimethylation of primary aliphatic amines in excellent yields at 40-100 °C with good tolerance to reducible functional groups. The catalytic intermediate CpRu(dpePhos)H was isolated and was shown to be active for methylation in the absence of base.
- Dang, Tuan Thanh,Ramalingam, Balamurugan,Seayad, Abdul Majeed
-
p. 4082 - 4088
(2015/11/11)
-
- Mn(ii) acetate: An efficient and versatile oxidation catalyst for alcohols
-
A homogeneous catalytic system consisting of Mn(ii) acetate (18 μmol), tert-butylhydroperoxide (2.5 mmol), acetonitrile (1.5 mL) and trifluoroacetic acid (91 μmol) was developed for efficient and selective oxidation of various alcohols (1 mmol). The system yielded good to quantitative conversions (42-100%) of various secondary alcohols, such as 2-octanol, fenchyl alcohol and borneol, to their corresponding ketones. Primary alcohols, for example 1-octanol and differently substituted benzyl alcohols, were mainly converted to their corresponding carboxylic acids. Studies with a selection of hydrocarbons, tertiary amines and a cyclic ether isochroman showed that besides alcohols, other substrates can be oxidised as well.
- Raeisaenen, Minna T.,Al-Hunaiti, Afnan,Atosuo, Elisa,Kemell, Marianna,Leskelae, Markku,Repo, Timo
-
p. 2564 - 2573
(2014/07/22)
-
- A facile and practical copper powder-catalyzed, organic solvent-and ligand-free ullmann amination of aryl halides
-
A facile and practical method that the copper powder-catalyzed Ullmann amination of aryl halides with aqueous methylamine under organic solvent-and ligand-free condition at 100 °C and in air gave N-arylamines as sole products in good to excellent yields. The presence of a small amount of air is essential. Other aliphatic primary amines show good to very high reactivity. Secondary amines and aniline are not reactive. Sensitive substituents (i.e., CHO, MeCO, CN and Cl) are tolerable in the reaction.
- Jiao, Jiao,Zhang, Xi-Ru,Chang, Ning-Hui,Wang, Jie,Wei, Jun-Fa,Shi, Xian-Ying,Chen, Zhan-Guo
-
supporting information; experimental part
p. 1180 - 1183
(2011/04/24)
-
- The effect of substitution on the utility of piperidines and octahydroindoles for reversible hydrogen storage
-
Substituted piperidines and octahydroindoles are compared in terms of their usability as reversible organic hydrogen storage liquids for hydrogen-powered fuel cells. Theoretical Gaussian calculations indicate which structural features are likely to lower the enthalpy of dehydrogenation. Experimental results show that attaching electron donating or conjugated substituents to the piperidine ring greatly increases the rate of catalytic dehydrogenation, with the greatest rates being observed with 4-aminopiperidine and piperidine-4-carboxamide. Undesired side reactions were observed with some compounds such as alkyl transfer reactions during the dehydrogenation of 4-dimethylaminopiperidine, C-O and C-N cleavage reactions during hydrogenation and/or subsequent dehydrogenation of 4-alkoxy and 4-amino indoles, and disproportionation during the hydrogenation of 4-aminopyridine. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
- Cui, Yi,Kwok, Samantha,Bucholtz, Andrew,Davis, Boyd,Whitney, Ralph A.,Jessop, Philip G.
-
p. 1027 - 1037
(2008/12/20)
-
- Homolytic aromatic substitution: A radical approach towards the synthesis of 5-azaoxindoles
-
A range of 5-azaoxindoles have been synthesised employing homolytic aromatic substitution onto pyridine as the pivotal step.
- Storey, John M.D.,Ladwa, Mitesh M.
-
p. 381 - 383
(2007/10/03)
-
- Quinazolines as MMP-13 inhibitors
-
A compound selected from those of formula (I): in which: R1 represents a group selected from hydrogen, amino, alkyl, alkenyl, aminoalkyl, aryl, arylalkyl, heterocycle, and cycloalkylalkyl, optionally substituted, W represents oxygen, sulfhur, or ═N—R′, in which R′ is as defined in the description, X1, X2 and X3 represent nitrogen or —C—R6 in which R6 is as defined in the description, Y represents oxygen, sulfhur, —NH, or —N(C1-C6)alkyl, Z represents oxygen, sulfhur, —NR7 in which R7 is as defined in the description, and 59 optionally carbon atom, n is an integer from 1 to 8 inclusive, Z1 represents —CR8R9 wherein R8 and R9 are as defined in the description, A represents aromatic or non-aromatic, heterocyclic or non-heterocyclic ring system, m is an integer from 0 to 7 inclusive, the group(s) R2 is (are) is as defined in the description, R3 represents hydrogen, alkyl, alkenyl, alkynyl, ot a group of formula: in which Z2, B, R5, P and q are as defined in the description, optionally, the racemic forms thereof, isomers thereof, N-oxydes thereof, and the pharmaceutically acceptable salts thereof, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.
- -
-
-
- Dialkylaminopyridine catalysed esterolysis of p-nitrophenyl alkanoates in different cationic microemulsions
-
The reactions of p-nitrophenyl alkanoate esters with dialkylaminopyridine (DAAP) and its related mono- and di-anionic water-soluble derivatives have been studied separately in three different microemulsion (ME) media.These were (a) oil-in-water ME (O/W),
- Bhattacharya, Santanu,Snehalatha, Karnam
-
p. 2021 - 2026
(2007/10/03)
-
- The Structure and Reactivity of 1,2,3,3-Tetrakis(4-(dimethylamino)pyridinium-1-yl)cyclopropene
-
The X-ray single crystal structure of 1,2,3,3-tetrakis(4-(dimethylamino)pyridinium-1-yl)cyclopropene, 1, is presented together with some reactions of 1.Both triphenylphosphine and 1-methylimidazole react with 1 to form the ring opened products, (Z)-1-(tri
- Feng, Amy S.,Speer, Drew V.,DiMagno, Stephen G.,Konings, Mark S.,Streitwieser, Andrew
-
p. 2902 - 2909
(2007/10/02)
-
- 2,2'-Diphenyl-Δ3,3'-bi-3H-indole-1,1'-dioxide: Competitive Demethylation and Redox Reactions
-
Competitve demethylation and redox reactions induced by 2,2'-diphenyl-Δ3,3'-bi-3H-indole-1,1'-dioxide, 1 (dinitrone) on several nitrogen bearing compounds (pyridines, amides, indoles, hydrazones and amines) are reported. - Keywords: 2,2'-Diphenyl-Δ3,3'-bi-3H-indole-1,1'-dioxide; Demethylation; Oxidation
- Bruni, Paolo,Conti, Carla,Tosi, Giorgio
-
p. 1311 - 1316
(2007/10/02)
-
- An Intramolecular Rearrangement in the Acetylation of Pyridin-4-amine
-
The surprisingly rapid formation of 4-(acetylamino)pyridine from reaction of pyridin-4-amine with various acetylating agents seems explicable by a mechanism which involves rate-determining intramolecular rearrangement of a first-formed ring N-acetyl intermediate.
- Deady, Leslie W.,Finlayson, Wayne L.
-
p. 429 - 433
(2007/10/02)
-
- Sodium Borohydride Reduction of Adducts of Primary Amines with Aldehydes and p-Thiocresol. The Alkylation of Heterocyclic and Aromatic Amino-compounds
-
p-Nitroaniline, 2-aminopyridine (1a), 4-aminopyridine (2a), 2-amino-4-methylpyrimidine (8a), 2-aminothiazole (10a), and 2-aminobenzimidazole (12a) react with aqueous formaldehyde and p-thiocresol in ethanol or methanol solution to give N-(p-tolylthiomethyl) derivatives , usually in high yields.When the latter compounds are heated, under reflux, with an excess of sodium borohydride in ethanol or 1,2-dimethoxyethane solution, the corresponding methylamino-compounds are obtained.By a similar two-step prosedure in which aqueous formaldehyde is replaced, as appropriate, by anhydrous acetaldehyde, propionaldehyde, or benzaldehyde, p-nitroaniline is converted into N-ethyl-p-nitroaniline, p-chloroaniline is converted into p-chloro-N-(n-propyl)aniline, (1a) is converted into the corresponding ethylamino- and benzylamino-compounds (1c) and (1d), respectively, and (10a) and (12a) are converted into their 2-N-(n-propyl) derivatives (10c) and (12c), respectively.
- Kemal, Oeznur,Reese, Colin B.
-
p. 1569 - 1573
(2007/10/02)
-
- Reactions of N-Heteroaromatic Bases with Nitrous Acid. Part 6. Kinetics of the Nitrosation of 2- and 4-Methylaminpprridine and their 1-Oxide Derivates
-
The nitrosation of 2- and 4-methylaminopyridine and their 1-oxide derivates in 0.002-5.00 M-perchoric acid is of first order in a both the amine and nitrous acid.The respective nitrosamines formed are easily denitrosated under the experimental conditions.The rate coefficients of the nitrosation increase with an increase in the concenration of perchloric acid and sodium perchlorate.In perchloric acid solution whose ionic strength is maintained constant by the addition of sodium perchlorate the rate coefficients of the nitrosation of 2- and 4-methylaminopyridine only show rectilinear dependence on the h0 parameter of the medium.The nitrosation of 2- and 4-methylaminopyridine proceeds mainly by the interaction of the nitrous acidium ion with the protonated form of these amines whilst the nitrosation of 2- and 4-methylaminopyridine 1-oxide proceeds by the simultaneous interaction of the nitrous acidium ion with the protonated and the free form of both amines.The nitrous acidium ion seems to show a distinct discrimination in its reaction with free form of the amines as evidenced by a rectilinear relationship between the rate coefficient of ther nitrosation and their Ka values.The protonated amine 1-oxides react faster than the protonated amines when the hydroxy-group is in para-position with respect to the amino-group and therefore not involved in hydrogen bonding with it.The nitrosation of free and the protonated amines involves an initial interaction between the nitrosating agent and the heteroaromatic nucleus.The present results show that the formation of the respective N-nitroso-derivate is the rate-determining stage of the diazotisation of the N-heteroaromatic amines over the whole of the acid range examined. pKa Values are recorded.
- Kalatzis, Evangelos,Papadopoulos, Panayiotis
-
p. 239 - 247
(2007/10/02)
-
- Process for the preparation of aminopyridines
-
A process for the preparation of aminopyridines of the formula STR1 wherein R1 and R2 are identical or different and are hydrogen or lower alkyl or, together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered heterocyclic ring containing up to 2 more hetero atoms, comprises reacting 4-pyridylpyridinium chloride or a salt thereof, at an elevated temperature, with an acid amide of the formula STR2 wherein R1 and R2 are as above and Z is --CO--R3 wherein R3 is hydrogen, lower alkyl, STR3 and R4 and R5 are hydrogen or lower alkyl.
- -
-
-
