- N-Methylation of p-Anisidine on the Catalysts Based on Cu-Containing Layered Double Hydroxides
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Abstract: Cu-containing layered double hydroxides with different Cu : Al ratios are synthesized by co-precipitation using a mixture of hydroxide and sodium carbonate as a precipitation agent. The influence of the precipitation agent concentration on the formation of the hydrotalcite phase was studied by thermal analysis and X-ray diffraction. The surface of the obtained samples after calcination at 450°C and their subsequent reduction at 300°C in hydrogen, was characterized by X-ray photoelectron spectroscopy and transmission electron microscopy. The synthesized catalysts were tested in the reaction of N-methylation of p-anisidine with methanol in an autoclave reactor to produce N-methyl-p-anisidine. The influence of the Cu : Al ratio in them on the catalytic activity and selectivity was studied.
- Bukhtiyarova,Nuzhdin,Kardash, T. Yu.,Bukhtiyarov,Gerasimov, E. Yu.,Romanenko
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- Cu layered double hydroxides as catalysts for N-methylation of p-anisidine: Influence of synthesis conditions
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Cu-containing layered double hydroxides were synthesized by co-precipitation method using base solution (NaOH and Na2CO3) with different concentration of carbonate ions. The influence of the precipitating agent concentration on formation of hydrotalcite phase was investigated. Characterization of the surface of the obtained samples calcined at 450 °C and 650 °C was performed by x-ray photoelectron spectroscopy. Catalysts based on Cu-layered double hydroxides were investigated in N-methylation of p-anisidine by methanol obtaining N-methyl-p-anisidine using autoclave reactor. Effect of precipitating agent concentration during synthesis of the Cu-layered double hydroxide on the catalyst performance was studied.
- Bukhtiyarova,Nuzhdin,Bukhtiyarov,Kardash,Romanenko
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- AQ-4, a deuterium-containing molecule, acts as a microtubule-targeting agent for cancer treatment
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The important physiological function of microtubules makes them an indispensable and clinically effective target of anti-tumor agents. Herein, we sought to design, synthesize, and evaluate a novel 4-anilinoquinazoline derivative and identify its anti-tumor activity in vitro and in vivo. The novel compound, N-(4-methoxyphenyl)-N-methyl-2-(methyl-d3)quinazolin-4-amine (AQ-4), was identified as a representative scaffold and potent microtubule-targeting agent. As a promising antimitotic agent, AQ-4 displayed remarkable anti-tumor activity with an average IC50 value of 19 nM across a panel of 14 human cancer cell lines. AQ-4 also exhibited nearly identical potent activities against drug-resistant cells, with no evidence of toxicity towards normal cells. A further target verification study revealed that AQ-4 targets the tubulin-microtubule system by significantly inhibiting tubulin polymerization and disrupting the intracellular microtubule spindle dynamics. According to the results of mechanism study, AQ-4 induced cell cycle arrest in the G2/M phase, promoting evident apoptosis and a collapses of mitochondrial membrane potential. The superior anti-tumor effect of AQ-4 in vivo suggests that it should be further investigated to validate its use for cancer therapy.
- Chen, Hua-Lin,Gong, Sha,Hu, Ya-Guang,Huang, Hui,Lin, Bi-Yun,Liu, Wen-Lin,Lu, Yuan-Zhi,Meng, Yu-Hua,Yan, Jun
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- A Mild Heteroatom (O -, N -, and S -) Methylation Protocol Using Trimethyl Phosphate (TMP)-Ca(OH) 2Combination
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A mild heteroatom methylation protocol using trimethyl phosphate (TMP)-Ca(OH)2combination has been developed, which proceeds in DMF, or water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol make it an attractive alternative to the conventional base-promoted heteroatom methylation procedures.
- Tang, Yu,Yu, Biao
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- Borane-Trimethylamine Complex as a Reducing Agent for Selective Methylation and Formylation of Amines with CO2
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We report herein that a borane-trimethylamine complex worked as an efficient reducing agent for the selective methylation and formylation of amines with 1 atm CO2 under metal-free conditions. 6-Amino-2-picoline serves as a highly efficient catalyst for the methylation of various secondary amines, whereas in its absence, the formylation of primary and secondary amines was achieved in high yield with high chemoselectivity. Mechanistic studies suggest that the 6-amino-2-picoline-borane catalytic system operates like an intramolecular frustrated Lewis pair to activate CO2.
- Zhang, Yanmeng,Zhang, He,Gao, Ke
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supporting information
p. 8282 - 8286
(2021/10/25)
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- Biobased Spiroimides from Itaconic Acid and Formamides: Molecular Targets for a Novel Synthetic Application of Renewable Chemicals
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Spiroimides exhibit a wide range of biological activities, such as anticonvulsant, antiarrhythmic, and antihyperglycemic activities. Herein, a novel synthetic application of renewable chemicals, itaconic acid and formamides, is described. Proper exploitation of the reactivity of itaconic acid and formamide allows for the development of an efficient synthetic approach for the production of several new biobased spiroimides, spiro[dihydroquinolin-2-one-succinimides] and spiro[indolin-2-one-glutarimides], in excellent overall yields (up to 98%).
- Hornink, Milene Macedo,Lopes, Alice Uva,Andrade, Leandro Helgueira
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supporting information
p. 296 - 308
(2020/11/09)
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- CO2-tuned highly selective reduction of formamides to the corresponding methylamines
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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
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supporting information
p. 7534 - 7538
(2021/10/12)
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- Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes
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Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410 nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.
- Cheng, Hanchao,Lam, Tsz-Lung,Liu, Yungen,Tang, Zhou,Che, Chi-Ming
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supporting information
p. 1383 - 1389
(2020/11/30)
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- Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol
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Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.
- Sarki, Naina,Goyal, Vishakha,Tyagi, Nitin Kumar,Puttaswamy,Narani, Anand,Ray, Anjan,Natte, Kishore
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p. 1722 - 1729
(2021/04/19)
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- Method for realizing N-alkylation by using alcohols as carbon source under photocatalysis
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The invention discloses a method for realizing N-alkylation by using alcohols as a carbon source under photocatalysis, and belongs to the technical field of catalytic synthesis. Alcohol, a substrate raw material and a catalyst are placed in a reaction device, ultraviolet and/or visible light irradiation is carried out in an inert atmosphere, after the irradiation is finished, solid-liquid separation is carried out to remove the catalyst, and an N-alkylation product can be obtained through extraction, distillation and purification, wherein the substrate raw material comprises any one of an amine compound, an aromatic nitro compound or an aromatic nitrile compound, the alcohol comprises any one or more of soluble primary alcohols, and the catalyst is metal oxide/titanium dioxide or metal sulfide/titanium dioxide. The method is simple and easy to operate, can be used for efficient photocatalysis one-pot multi-step hydrogenation N-alkylation reaction, and is mild in reaction condition, high in chemical selectivity of N-alkylamine, good in catalyst stability and easy to recycle.
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Paragraph 0048-0057
(2021/03/13)
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- Additive-freeN-methylation of amines with methanol over supported iridium catalyst
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An efficient and versatile zinc oxide-supported iridium (Ir/ZnO) catalyst was developed to catalyze the additive-freeN-methylation of amines with methanol. Mechanistic studies suggested that the high catalytic reactivity is rooted in the small sizes (1.4 nm) of Ir nanoparticles and the high ratio (93%) of oxidized iridium species (IrOx, Ir3+and Ir4+) on the catalyst. Moreover, the delicate cooperation between the IrOxand ZnO support also promoted its high reactivity. The selectivity of this catalyticN-methylation was controllable between dimethylation and monomethylation by carefully tuning the catalyst loading and reaction solvent. Specifically, neat methanol with high catalyst loading (2 mol% Ir) favored the formation ofN,N-dimethylated amine, while the mesitylene/methanol mixture with low catalyst loading (0.5 mol% Ir) was prone to producing mono-N-methylated amines. An environmentally benign continuous flow system with a recycled mode was also developed for the efficient production ofN-methylated amines. With optimal flow rates and amine concentrations, a variety ofN-methylamines were produced with good to excellent yields in this Ir/ZnO-based flow system, providing a starting point for the clean and efficient production ofN-methylamines with this cost-effective chemical process.
- Liu, Xiang,Loh, Teck-Peng,Qiang, Wenwen,Wang, Jing,Ye, Sen,Zhu, Longfei
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p. 3364 - 3375
(2021/06/06)
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- Synthesis of N-Alkyl Anilines from Arenes via Iron-Promoted Aromatic C-H Amination
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We report both an intermolecular C-H amination of arenes to access N-methylanilines and an intramolecular variant for the synthesis of tetrahydroquinolines. A newly developed, highly electrophilic aminating reagent was key for the direct synthesis of unprotected N-methylanilines from simple arenes. The reactions display a broad functional group tolerance and employ catalytic amounts of a benign iron salt under mild reaction conditions.
- Falk, Eric,Gasser, Valentina C. M.,Morandi, Bill
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supporting information
p. 1422 - 1426
(2021/03/08)
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- Photocatalytic Water-Splitting Coupled with Alkanol Oxidation for Selective N-alkylation Reactions over Carbon Nitride
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Photocatalytic water splitting technology (PWST) enables the direct use of water as appealing “liquid hydrogen source” for transfer hydrogenation reactions. Currently, the development of PWST-based transfer hydrogenations is still in an embryonic stage. Previous reports generally centered on the rational utilization of the in situ generated H-source (electrons) for hydrogenations, in which photogenerated holes were quenched by sacrificial reagents. Herein, the fully-utilization of the liquid H-source and holes during water splitting is presented for photo-reductive N-alkylation of nitro-aromatic compounds. In this integrate system, H-species in situ generated from water splitting were designed for nitroarenes reduction to produce amines, while alkanols were oxidized by holes for cascade alkylating of anilines as well as the generated secondary amines. More than 50 examples achieved with a broad range scope validate the universal applicability of this mild and sustainable coupling approach. The synthetic utility of this protocol was further demonstrated by the synthesis of existing pharmaceuticals via selective N-alkylation of amines. This strategy based on the sustainable water splitting technology highlights a significant and promising route for selective synthesis of valuable N-alkylated fine chemicals and pharmaceuticals from nitroarenes and amines with water and alkanols.
- Xu, Yangsen,Zhang, Zhaofei,Qiu, Chuntian,Chen, Shaoqin,Ling, Xiang,Su, Chenliang
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p. 582 - 589
(2020/12/09)
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- A Metal-Free Direct Arene C?H Amination
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The synthesis of aryl amines via the formation of a C?N bond is an essential tool for the preparation of functional materials, active pharmaceutical ingredients and bioactive products. Usually, this chemical connection is only possible by transition metal-catalyzed reactions, photochemistry or electrochemistry. Here, we report a metal-free arene C?H amination using hydroxylamine derivatives under benign conditions. A charge transfer interaction between the aminating reagents TsONHR and the arene substrates enables the chemoselective amination of the arene, even in the presence of various functional groups. Oxygen was crucial for an effective conversion and its accelerating role for the electron transfer step was proven experimentally. In addition, this was rationalized by a theoretical study which indicated the involvement of a dioxygen-bridged complex with a “Sandwich-like” arrangement of the aromatic starting materials and the aminating agents at the dioxygen molecule. (Figure presented.).
- Wang, Tao,Hoffmann, Marvin,Dreuw, Andreas,Hasagi?, Edina,Hu, Chao,Stein, Philipp M.,Witzel, Sina,Shi, Hongwei,Yang, Yangyang,Rudolph, Matthias,Stuck, Fabian,Rominger, Frank,Kerscher, Marion,Comba, Peter,Hashmi, A. Stephen K.
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supporting information
p. 2783 - 2795
(2021/04/05)
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- Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
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Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
- Zhao, Chenxi,Tang, Chu,Li, Changhao,Ning, Wentao,Hu, Zhiye,Xin, Lilan,Zhou, Hai-Bing,Huang, Jian
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- Effect of the ancillary ligand in N-heterocyclic carbene iridium(III) catalyzed N-alkylation of amines with alcohols
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A series of air-stable N-heterocyclic carbene (NHC) Ir(III) complexes (Ir1-6), bearing various combinations of chlorine, pyridine and NHC ligands, were assayed for the N-alkylation of amines with alcohols. It was found that Ir3, with two monodentate 1,3-bis-methyl-imidazolylidene (IMe) ligands, emerged as the most active complex. A large variety of amines and primary alcohols were efficiently converted into mono-N-alkylated amines in 53–96% yields. As a special highlight, for the challenging MeOH, selective N-monomethylation could be achieved using KOH as a base under an air atmosphere. Moreover, this catalytic system was successfully applied to the gram-scale synthesis of some valuable compounds.
- Feng, Xinshu,Huang, Ming
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- Ruthenium(ii) complexes with N-heterocyclic carbene-phosphine ligands for theN-alkylation of amines with alcohols
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Metal hydride complexes are key intermediates forN-alkylation of amines with alcohols by the borrowing hydrogen/hydrogen autotransfer (BH/HA) strategy. Reactivity tuning of metal hydride complexes could adjust the dehydrogenation of alcohols and the hydrogenation of imines. Herein we report ruthenium(ii) complexes with hetero-bidentate N-heterocyclic carbene (NHC)-phosphine ligands, which realize smart pathway selection in theN-alkylated reactionviareactivity tuning of [Ru-H] species by hetero-bidentate ligands. In particular, complex6cbwith a phenyl wingtip group and BArF?counter anion, is shown to be one of the most efficient pre-catalysts for this transformation (temperature is as low as 70 °C, neat conditions and catalyst loading is as low as 0.25 mol%). A large variety of (hetero)aromatic amines and primary alcohols were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields. Notably, aliphatic amines, challenging methanol and diamines could also be transformed into the desired products. Detailed control experiments and density functional theory (DFT) calculations provide insights to understand the mechanism and the smart pathway selectionvia[Ru-H] species in this process.
- Huang, Ming,Li, Yinwu,Lan, Xiao-Bing,Liu, Jiahao,Zhao, Cunyuan,Liu, Yan,Ke, Zhuofeng
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supporting information
p. 3451 - 3461
(2021/05/03)
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- Ru-Catalyzed Selective Catalytic Methylation and Methylenation Reaction Employing Methanol as the C1 Source
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Methanol can be employed as a green and sustainable methylating agent to form C-C and C-N bonds via borrowing hydrogen (BH) methodology. Herein we explored the activity of the acridine-derived SNS-Ru pincer for the activation of methanol to apply it as a C1 building block in different reactions. Our catalytic system shows great success toward the β-C(sp3)-methylation reaction of 2-phenylethanols to provide good to excellent yields of the methylated products. We investigated the mechanistic details, kinetic progress, and temperature-dependent product distribution, which revealed the slow and steady generation of in situ formed aldehyde, is the key factor to get the higher yield of the β-methylated product. To establish the environmental benefit of this reaction, green chemistry metrics are calculated. Furthermore, dimerization of 2-naphthol via methylene linkage and formation of N-methylation of amine are also described in this study, which offers a wide range of substrate scope with a good to excellent yield.
- Biswas, Nandita,Srimani, Dipankar
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p. 10544 - 10554
(2021/07/31)
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- Efficient methylation of anilines with methanol catalysed by cyclometalated ruthenium complexes
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Cyclometalated ruthenium complexes4-10allow the effective methylation of anilines with methanol to selectively giveN-methylanilines. This hydrogen autotransfer procedure proceeds under mild conditions (60 °C) in a practical manner (NaOH as base). Mechanistic investigations suggest an active homogenous ruthenium complex and β-hydride elimination of methanol as the rate determining step.
- Piehl, Patrick,Amuso, Roberta,Spannenberg, Anke,Gabriele, Bartolo,Neumann, Helfried,Beller, Matthias
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p. 2512 - 2517
(2021/04/22)
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- N-Methylation of Amines with Methanol in the Presence of Carbonate Salt Catalyzed by a Metal-Ligand Bifunctional Ruthenium Catalyst [(p-cymene)Ru(2,2′-bpyO)(H2O)]
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A ruthenium complex [(p-cymene)Ru(2,2′-bpyO)(H2O)] was found to be a general and efficient catalyst for the N-methylation of amines with methanol in the presence of carbonate salt. Moreover, a series of sensitive substituents, such as nitro, ester, cyano, and vinyl groups, were tolerated under present conditions. It was confirmed that OH units in the ligand are crucial for the catalytic activity. Notably, this research exhibited the potential of metal-ligand bifunctional ruthenium catalysts for the hydrogen autotransfer process.
- Liu, Peng,Tung, Nguyen Thanh,Xu, Xiangchao,Yang, Jiazhi,Li, Feng
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p. 2621 - 2631
(2021/02/27)
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- Recyclable covalent triazine framework-supported iridium catalyst for the N-methylation of amines with methanol in the presence of carbonate
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An iridium complex Cp*Ir@CTF, which is synthesized by the coordinative immobilization of [Cp*IrCl2]2 on a functionalized covalent triazine framework (CTF), was found to be a general and highly efficient catalyst for the N-methylation of amines with methanol in the presence of carbonate. Under environmentally benign conditions, a variety of desirable products were obtained in high yields with complete selectivities and functional group friendliness. Furthermore, the synthesized catalyst could be recycled by simple filtration without obvious loss of catalytic activity after sixth cycle. Notably, this research exhibited the potential of covalent triazine framework-supported transition metal catalysts for hydrogen autotransfer process.
- Liu, Peng,Yang, Jiazhi,Ai, Yao,Hao, Shushu,Chen, Xiaozhong,Li, Feng
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p. 281 - 290
(2021/03/26)
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- Electrosynthesis of Dihydropyrano[4,3-b]indoles Based on a Double Oxidative [3+3] Cycloaddition
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Oxidative [3+3] cycloadditions offer an efficient route for six-membered-ring formation. This approach has been realized based on an electrochemical oxidative coupling of indoles/enamines with active methylene compounds followed by tandem 6π-electrocyclization leading to the synthesis of dihydropyrano[4,3-b]indoles and 2,3-dihydrofurans. The radical–radical cross-coupling of the radical species generated by anodic oxidation combined with the cathodic generation of the base from O2 allows for mild reaction conditions for the synthesis of structurally complex heterocycles.
- Choi, Subin,Park, Cheol-Min,Park, Jinhwi,Sim, Jeongwoo,Yu, Eunsoo
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supporting information
p. 11886 - 11891
(2020/05/22)
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- Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor
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Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KOtBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of N-methyl-N-arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction. The HE anion can be easily prepared in situ by reaction of the corresponding HE with KOtBu in DMSO at rt. Both protocols were further explored in terms of synthetic scope as well as mechanistic aspects to rationalize key features of desulfonylation processes. Furthermore, the HE anion induces reductive dehalogenation reaction of aryl halides under visible light irradiation.
- Heredia, Micaela D.,Guerra, Walter D.,Barolo, Silvia M.,Fornasier, Santiago J.,Rossi, Roberto A.,Budén, Mariá E.
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supporting information
p. 13481 - 13494
(2020/12/15)
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- P(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate
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The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
- Li, Gen,Qin, Ziyang,Radosevich, Alexander T.
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p. 16205 - 16210
(2020/10/26)
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- Synthesis of: N -methylated amines from acyl azides using methanol
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The transformation of acyl azide derivatives into N-methylamines was developed using methanol as the C1 source via the one-pot Curtius rearrangement and borrowing hydrogen methodology. Following this protocol, various functionalised N-methylated amines were synthesized using the (NNN)Ru(ii) complex from carboxylic acids via an acyl azide intermediate. Several kinetic studies and DFT calculations were carried out to support the mechanism and also to determine the role of the Ru(ii) complex and base in this transformation.
- Chakrabarti, Kaushik,Dutta, Kuheli,Kundu, Sabuj
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p. 5891 - 5896
(2020/08/21)
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- Selective N -monomethylation of primary anilines with the controllable installation of N -CH2D, N -CHD2, and N -CD3units
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The selective N-monomethylation of primary anilines was realized by the use of the Me3N-BH3/N,N-dimethylformamide (DMF) system as the methyl source. This method also allows for the controllable introduction of N-CH2D, N-CHD2, and N-CD3 units with high lev
- Meng, Jing,Wang, Yi-Feng,Wang, Zhijuan,Xia, Hui-Min,Xu, Ai-Qing,Zhang, Feng-Lian
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supporting information
p. 4922 - 4926
(2020/07/30)
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- EffectiveN-methylation of nitroarenes with methanol catalyzed by a functionalized NHC-based iridium catalyst: a green approach toN-methyl amines
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Compound [IrBr(CO)2(κC-tBuImCH2PyCH2OMe)] featuring a flexible pyridine/OMe functionalized NHC ligand κ1C coordinated efficiently catalyzes the selectiveN-monomethylation of nitroarenes using methanol as both the reducing agent and the C1 source. A range of functionalized nitroarenes including heterocyclic or sterically hindered derivatives have been efficiently converted to the correspondingN-monomethyl amines in good yields at low catalyst loadings using sub-stoichiometric amounts of Cs2CO3as a base. Mechanistic investigations support a borrowing-hydrogen mechanism in which methanol acts as the hydrogen source and methylating agent. Further, the hydrogen transfer reduction of nitrobenzene to aniline under optimized reaction conditions should proceed through a direct mechanism involving nitrosobenzene andN-phenylhydroxylamine intermediates.
- González-Lainez, Miguel,Jiménez, M. Victoria,Passarelli, Vincenzo,Pérez-Torrente, Jesús J.
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p. 3458 - 3467
(2020/06/17)
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- Highly Efficient Binuclear Copper-catalyzed Oxidation of N,N-Dimethylanilines with O2
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A binuclear copper-salicylate complex, [Cu(Sal)2(NCMe)]2 (Sal=salicylate), was found to be an active catalyst for the oxidation of N,N-dimethylanilines by O2, affording the corresponding N-methyl-N-phenylformamides as major products. The reactions were carried out with a O2 balloon and the S/C (substrate/catalyst ratio) of the model reaction could be up to 1×105, providing a practical and highly efficient catalytic protocol for accessing N-methyl-N-phenylformamides.
- Liu, Yuxia,Yan, Yonggang,Xue, Dong,Wang, Zhongfu,Xiao, Jianliang,Wang, Chao
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p. 2221 - 2225
(2020/03/23)
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- Bimetallic Bis-NHC-Ir(III) Complex Bearing 2-Arylbenzo[d]oxazolyl Ligand: Synthesis, Catalysis, and Bimetallic Effects
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Herein, an unprecedented bimetallic bis-NHC Cp*Ir complex 1 bearing 2-arylbenzo[d]oxazolyl and NHC ligands is reported. A significant increase in activity was observed for N-methylation of amines and reduction of aldehydes with MeOH catalyzed by 1 compared to the monometallic analogues (2-11). Under the optimal conditions, it showed to be highly effective in N-methylation of nitroarenes with MeOH as both C1 and H2 source. Substrates, including aromatic amines, ketones, and nitro compounds with various functional groups, can be well-tolerated. Mechanistic studies and DFT calculation highlight the significance of bimetallic centers cooperativity.
- Huang, Shuang,Hong, Xi,Cui, He-Zhen,Zhan, Bing,Li, Zhi-Ming,Hou, Xiu-Feng
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p. 3514 - 3523
(2020/10/09)
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- Manganese-Catalyzed One-Pot Conversion of Nitroarenes into N-Methylarylamines Using Methanol
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A manganese-catalyzed one-pot conversion of nitroarenes into N-methylarylamines has been developed. This transfer hydrogenation method employs a well-defined bench stable Mn PN3P pincer precatalyst in combination with methanol as both the reductant and the C1 source. A selection of commercially available nitroarenes was converted into N-methylarylamines in synthetically useful yields.
- Mast, Nicolas,Morrill, Louis C.,Reed-Berendt, Benjamin G.
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supporting information
(2020/03/03)
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- Catalyst-Free Electrosynthesis of Benzimidazolones through Intramolecular Oxidative C?N Coupling
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The electrochemical synthesis of N, N’-disubstituted benzimidazolones from ureas through an intramolecular anodic dehydrogenative N?H/C?H coupling has been developed. The reaction undergoes under the undivided electrolysis conditions and obviates the need for any catalysts and chemical oxidants. (Figure presented.).
- Li, Jiang-Sheng,Yang, Pan-Pan,Xie, Xin-Yun,Jiang, Si,Tao, Li,Li, Zhi-Wei,Lu, Cui-Hong,Liu, Wei-Dong
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supporting information
p. 1977 - 1981
(2020/04/20)
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- Selective Pd-catalyzed monoarylation of small primary alkyl amines through backbone-modification in ylide-functionalized phosphines (YPhos)
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Ylide-substituted phosphines have been shown to be excellent ligands for C-N coupling reactions under mild reaction conditions. Here we report studies on the impact of the steric demand of the substituent in the ylide-backbone on the catalytic activity. Two new YPhos ligands with bulky ortho-tolyl (pinkYPhos) and mesityl (mesYPhos) substituents were synthesized, which are slightly more sterically demanding than their phenyl analogue but considerably less flexible. This change in the ligand design leads to higher selectivities and yields in the arylation of small primary amines compared to previously reported YPhos ligands. Even MeNH2 and EtNH2 could be coupled at room temperature with a series of aryl chlorides in high yields.
- Rodstein, Ilja,Prendes, Daniel Sowa,Wickert, Leon,Paa?en, Maurice,Gessner, Viktoria H.
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p. 14674 - 14683
(2020/12/29)
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- Esterification of Tertiary Amides: Remarkable Additive Effects of Potassium Alkoxides for Generating Hetero Manganese–Potassium Dinuclear Active Species
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A catalyst system of mononuclear manganese precursor 3 combined with potassium alkoxide served as a superior catalyst compared with our previously reported manganese homodinuclear catalyst 2 a for esterification of not only tertiary aryl amides, but also tertiary aliphatic amides. On the basis of stoichiometric reactions of 3 and potassium alkoxide salt, kinetic studies, and density functional theory (DFT) calculations, we clarified a plausible reaction mechanism in which in situ generated manganese–potassium heterodinuclear species cooperatively activates the carbonyl moiety of the amide and the OH moiety of the alcohols. We also revealed details of the reaction mechanism of our previous manganese homodinuclear system 2 a, and we found that the activation free energy (ΔG≠) for the manganese–potassium heterodinuclear complex catalyzed esterification of amides is lower than that for the manganese homodinuclear system, which was consistent with the experimental results. We further applied our catalyst system to deprotect the acetyl moiety of primary and secondary amines.
- Akiyama, Shoko,Himo, Fahmi,Hirai, Takahiro,Katayama, Shoichiro,Kato, Daiki,Mai, Binh Khanh,Mashima, Kazushi,Nagae, Haruki
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- Ruthenium(II) Complexes of Heteroditopic N-Heterocyclic Carbene Ligands: Efficient Catalysts for C-N Bond Formation via a Hydrogen-Borrowing Strategy under Solvent-Free Conditions
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Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating these ligands for C-N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating ligands integrated with ImNHC and mesoionic tzNHC donors connected via a CH2 spacer with a diverse triazole backbone. The synthesized ruthenium(II) complexes 3 are found to be highly efficient for C-N bond formation across a wide range of primary amine and alcohol substrates under solvent-free conditions, and among all of the complexes studied here, catalyst 3a with a mesityl substituent displayed maximum activity. To our delight, catalyst 3a is also effective for the selective mono-N-methylation of various anilines utilizing methanol as a coupling partner, known to be relatively more difficult than other alcohols. Furthermore, complex 3a also delivers various substituted quinolines successfully via the reaction of 2-aminobenzyl alcohol with several secondary alcohols. Importantly, catalyst 3a exhibited the highest activity among the reported ruthenium(II) complexes for both the N-benzylation of aniline [achieving a turnover number (TON) of 50000] and the realization of quinoline 8a by reacting 2-aminobenzyl alcohol with 2-phenylethanol (attaining a TON of 30000).
- Donthireddy,Mathoor Illam, Praseetha,Rit, Arnab
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supporting information
p. 1835 - 1847
(2020/01/31)
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- Comparison of the effect of N-methyl and N-aryl groups on the hydrolytic stability and electronic properties of betalain dyes
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Betalains are antioxidant secondary metabolites that emerged as safe color additives for food and cosmetics, fluorescent dyes, and redox mediators. Herein, we describe the semisynthesis of N-methyl phenylbetalain (mepBeets) and N-aryl phenylbetalain (dipBeets) dyes and compare the effect of the structure on their hydrolytic stability and electronic properties. Eight model compounds were semisynthesized by coupling betalamic acid with either N-methyl anilines or N-aryl anilines in ethyl acetate using p-toluenesulfonic acid as catalyst. The presence of electron-withdrawing substituents in the aryl moiety of mepBeets and dipBeets results in faster hydrolysis, lower anodic potentials and increased fluorescence quantum yields compared to the corresponding unsubstituted parent compounds. The results are rationalized by considering the charge distribution in the 1,7-diazaheptamethinium chromophore and are useful for the development of new hydrolytically stable betalain dyes with tunable redox and optical properties.
- Bastos, Erick Leite,Dochev, Stefan,Esteves, Larissa Cerrato,Mattioli, Renan Rodini,Pioli, Renan Moraes
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- Photon-initiated heterogeneous redox couples for methylation of anilines under mild conditions
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Methylation of anilines has drawn a lot of attention due to their valuable applications and directly using methanol as a methylation reagent is of great advantage. Photon-initiated heterogeneous catalysis of this methylation process meets the requirements of green chemistry. Herein we show that balanced redox zones within carbon nitride supported Pd nanoparticles boost the selectivity of methylation of anilines under mild conditions.
- Zhang, Bing,Gao, Hua,Wang, Wei
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p. 4433 - 4437
(2020/08/10)
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- METHOD FOR PRODUCING N-METHYL-PARA-ANISIDINE
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The invention relates to chemical engineering processes, and more particularly to liquid-phase catalytic methods for producing, in the presence of hydrogen, alkylated para-anisidine for use as a chemical substance or as a gasoline additive for increasing the octane rating of a gasoline. The technical result of the claimed group of inventions is an increase in the yield of N-methyl-para-anisidine and a decrease in the yield of a dimethyl derivative. A method for producing N-methyl-para-anisidine in a liquid phase includes alkylating para-anisidine with formalin as they are separately, simultaneously fed into a mixer disposed in a reactor, directly upstream of a catalytic reduction zone, thus producing an intermediate azomethine, and subsequently reducing same on a hydrogenation catalyst at a temperature of 20-120° C. in an environment of hydrogen at elevated pressure, and then isolating the target product, N-methyl-para-anisidine.
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Paragraph 0071-0073; 0077-0088
(2019/08/18)
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- Highly selective hydrogenation of amides catalysed by a molybdenum pincer complex: Scope and mechanism
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A series of molybdenum pincer complexes has been shown for the first time to be active in the catalytic hydrogenation of amides. Among the tested catalysts, Mo-1a proved to be particularly well suited for the selective C-N hydrogenolysis of N-methylated formanilides. Notably, high chemoselectivity was observed in the presence of certain reducible groups including even other amides. The general catalytic performance as well as selectivity issues could be rationalized taking an anionic Mo(0) as the active species. The interplay between the amide CO reduction and the catalyst poisoning by primary amides accounts for the selective hydrogenation of N-methylated formanilides. The catalyst resting state was found to be a Mo-alkoxo complex formed by reaction with the alcohol product. This species plays two opposed roles-it facilitates the protolytic cleavage of the C-N bond but it encumbers the activation of hydrogen.
- Leischner, Thomas,Artús Suarez, Lluis,Spannenberg, Anke,Junge, Kathrin,Nova, Ainara,Beller, Matthias
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p. 10566 - 10576
(2019/12/02)
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- Iron-Catalyzed Regioselective α-C-H Alkylation of N-Methylanilines: Cross-Dehydrogenative Coupling between Unactivated C(sp3)-H and C(sp3)-H Bonds via a Radical Process
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The iron-catalyzed α-C-H alkylation of N-methylanilines without any directing group by cross-dehydrogenative coupling between unactivated C(sp3)-H and C(sp3)-H bonds has been established for the first time, which provides a good complement to C(sp3)-H activation reactions and expands the field of Fe-catalyzed C-H functionalizations. Many different C(sp3)-H bonds in cyclic alkanes, cyclic ethers, and toluene derivatives can be used as coupling partners. Mechanistic investigations including the radical reaction process, the main role of various reagents, and the kinetic isotope effect experiment were also described.
- Li, Ze-Lin,Sun, Kang-Kang,Wu, Peng-Yu,Cai, Chun
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p. 6830 - 6839
(2019/06/14)
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- Catalytic Hydrogenation of Carboxamides with a Bifunctional Cp Ru Catalyst Bearing an Imidazol-2-ylidene with a Protic Aminoethyl Side Chain
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Synthesis of a Cp Ru complex bearing an NH 2 -functionalized N -heterocyclic carbene (C-N H) was achieved by treatment of CpRuBr(isoprene) with an equimolar amount of a silver complex, which was generated from Ag 2 O and 1-(2-aminoethyl)-3-methylimidazolium bromide, in CH 3 CN at room temperature. The new CpRuBr(C-N H) complex showed a higher catalytic performance than the related CpRuCl(P-N H) and CpRuCl(N-N H) complexes. In the reaction of N -arylcarboxamides, the amine products were obtained in satisfactory yields under mild temperature conditions.
- Ikariya, Takao,Kawano, Teruhiro,Kayaki, Yoshihito,Watari, Ryo
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p. 2542 - 2547
(2019/06/08)
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- Selective formylation or methylation of amines using carbon dioxide catalysed by a rhodium perimidine-based NHC complex
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Carbon dioxide can play a vital role as a sustainable feedstock for chemical synthesis. To be viable, the employed protocol should be as mild as possible. Herein we report a methodology to incorporate CO2 into primary, secondary, aromatic or alkyl amines catalysed by a Rh(i) complex bearing a perimidine-based NHC/phosphine pincer ligand. The periminide-based ligand belongs to a class of 6-membered NHC ligand accessed through chelate-assisted double C-H activation. N-Formylation and -methylation of amines were performed using a balloon of CO2, and phenylsilane as the reducing agent. Product selectivity between formylated and methylated products was tuned by changing the solvent, reaction temperature and the quantity of phenylsilane used. Medium to excellent conversions, as well as tolerance to a range of functional groups, were achieved. Stoichiometric reactions with reactants employed in catalysis and time course studies suggested that formylation and methylation reactions of interest begin with hydrosilylation of CO2 followed by reaction with amine substrates.
- Lam, Raphael H.,McQueen, Caitlin M. A.,Pernik, Indrek,McBurney, Roy T.,Hill, Anthony F.,Messerle, Barbara A.
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supporting information
p. 538 - 549
(2019/02/14)
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- Palladium-Catalyzed Methylation of Nitroarenes with Methanol
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A procedure for the synthesis of N-methyl-arylamines directly from nitroarenes using methanol as green methylating agent was developed. The key to success is the use of a specific catalyst system consisting of palladium acetate and the ligand 1-[2,6-bis(isopropyl)phenyl]-2-[tert-butyl(2-pyridinyl)phosphino]-1H-Imidazole (L1). The generality of this protocol is demonstrated in the synthesis of more than 20 N-methyl-arylamines under comparably mild conditions. Combining this novel methodology with subsequent coupling processes using the same catalyst allows for efficient diversification of aromatic nitro compounds to a broad variety of amines including drug molecules.
- Wang, Lin,Neumann, Helfried,Beller, Matthias
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supporting information
p. 5417 - 5421
(2019/04/04)
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- N-Methylation of amines and nitroarenes with methanol using heterogeneous platinum catalysts
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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
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- Commercial Pd/C-Catalyzed N-Methylation of Nitroarenes and Amines Using Methanol as Both C1 and H2 Source
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Herein, we report commercially available carbon-supported-palladium (Pd/C)-catalyzed N-methylation of nitroarenes and amines using MeOH as both a C1 and a H2 source. This transformation proceeds with high atom-economy and in an environmentally friendly way via borrowing hydrogen mechanism. A total of >30 structurally diverse N-methylamines, including bioactive compounds, were selectively synthesized with isolated yields of up to 95%. Furthermore, selective N-methylation and deuteration of nimesulide, a nonsteroidal anti-inflammatory drug, were realized through the late-stage functionalization.
- Goyal, Vishakha,Gahtori, Jyoti,Narani, Anand,Gupta, Piyush,Bordoloi, Ankur,Natte, Kishore
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p. 15389 - 15398
(2019/12/04)
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- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
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The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
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- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
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The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
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p. 14627 - 14635
(2019/12/02)
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- DIRECT C-H AMINATION AND AZA-ANNULATION
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In some aspects, the present disclosure provides methods of aminating an aromatic compound comprising reacting an aminating agent with an aromatic compound in the presence of a rhodium catalyst. In some embodiments, the methods may comprise aminating an aromatic compound which contains multiple different functional groups. The methods described herein may also be used to create bicyclic system comprising reacting an intramolecular aminating agent with an aromatic ring to obtain a second ring containing a nitrogen atom. In another aspect, the methods described herein may also be used to create a cyclic aliphatic cyclic/poly cyclic amine system comprising a reacting an intramolecular aminating agent by insertion into a C(sp3)-H bond.
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Paragraph 0132; 0154; 0155
(2019/06/07)
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- Room temperature N-heterocyclic carbene manganese catalyzed selective N-alkylation of anilines with alcohols
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The first example of room temperature non-noble metal homogeneous system catalyzed selective N-alkylation of anilines with alcohols by a bis-NHC manganese complex is presented. This system was applied to a large range of alcohols and anilines, including biologically relevant motifs and challenging methanol. Experimental and computational studies suggest an outer-sphere mechanism for this NHC-Mn system.
- Huang, Ming,Li, Yukui,Li, Yinwu,Liu, Jiahao,Shu, Siwei,Liu, Yan,Ke, Zhuofeng
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supporting information
p. 6213 - 6216
(2019/06/07)
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- N -Methylation of ortho -substituted aromatic amines with methanol catalyzed by 2-arylbenzo [d] oxazole NHC-Ir(iii) complexes
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Seven new chelated cyclometalated Ir complexes of ABON,P, ABON,O, and ABON,C(carbene) based on a rigid and tunable 2-arylbenzo[d]oxazole backbone have been prepared for the N-methylation of amines. Among these three coordinated modes, ABON,C(carbene)-chelated iridium-based catalysts exhibited good performance in the monomethylation of aromatic amines with methanol (MeOH) as the green methylation reagent. The steric-modified synthesis of ABON,C(carbene) complexes was described. The most active ABON,C(carbene) complex with marginal steric hindrance as a catalyst was obtained from the benzoxazole ring without a substituent and methyl group of the benzimidazole ring on the N-heterocyclic carbene (NHC) ligand. A variety of amines including para- and meta-substituted aromatic amines, as well as heterocyclic amines, were formulated as suitable substrates. Importantly, this catalyst considerably promoted the yield of the N-methylation of ortho-substituted aromatic amines. Controlled kinetic experiments and deuterium-labeling reactions of these ortho-substituted amines were conducted under optimized conditions. On the basis of the experimental results, a plausible mechanism was proposed.
- Huang, Shuang,Hong, Xi,Cui, He-Zhen,Zhou, Quan,Lin, Yue-Jian,Hou, Xiu-Feng
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p. 5072 - 5082
(2019/04/17)
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- Palladacycle-Phosphine Catalyzed Methylation of Amines and Ketones Using Methanol
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Methylation of amines and ketones with palladacycle precatalyst has been performed using methanol as an environmentally benign reagent. Various ketones and amines undergo methylation reaction to yield monomethylated amines or ketones in moderate to good isolated yields. Moreover, this protocol was tested for the chemoselective methylation of 4-aminobenzenesulfonamide. The scope of the reaction was further extended to the deuteromethylation of ketones.
- Mamidala, Ramesh,Biswal, Priyabrata,Subramani, M. Siva,Samser, Shaikh,Venkatasubbaiah, Krishnan
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p. 10472 - 10480
(2019/08/20)
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