- Borane-Trimethylamine Complex as a Reducing Agent for Selective Methylation and Formylation of Amines with CO2
-
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
-
supporting information
p. 8282 - 8286
(2021/10/25)
-
- Biobased Spiroimides from Itaconic Acid and Formamides: Molecular Targets for a Novel Synthetic Application of Renewable Chemicals
-
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
-
supporting information
p. 296 - 308
(2020/11/09)
-
- 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)
-
- Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
-
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
-
-
- Halogenated method of aromatic compound
-
The invention belongs to the field of organic synthesis, and particularly relates to synthesis of aromatic halogens, in particular to arylamine. The invention discloses a synthesis method of a corresponding ortho-halogenated product from aromatic compounds such as carbazole and phenol. The method comprises the following steps: adding a metal sulfonate salt catalyst, aromatic amine, carbazole, phenol and other hydrogen - heteroatom-containing aromatic compound reaction substrates, a halogenation reagent and a reaction solvent at a specific reaction temperature. After the drying agent is dried, the yield of the reaction product and the nuclear magnetic characterization determining structure are determined by column chromatography. The reaction product yield is determined by gas chromatography. By adopting the method, under the cheap metal salt catalyst, a plurality of ortho-substituted brominated and chloro products can be obtained with moderate to excellent yield.
- -
-
Paragraph 0034-0037; 0227-0229; 0238
(2021/11/10)
-
- Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes
-
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
-
supporting information
p. 1383 - 1389
(2020/11/30)
-
- 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)
-
- Synthesis of N-Alkyl Anilines from Arenes via Iron-Promoted Aromatic C-H Amination
-
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
-
supporting information
p. 1422 - 1426
(2021/03/08)
-
- Method for realizing N-alkylation by using alcohols as carbon source under photocatalysis
-
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.
- -
-
Paragraph 0048-0056; 0058
(2021/03/13)
-
- Photocatalytic Water-Splitting Coupled with Alkanol Oxidation for Selective N-alkylation Reactions over Carbon Nitride
-
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
-
p. 582 - 589
(2020/12/09)
-
- Effect of the ancillary ligand in N-heterocyclic carbene iridium(III) catalyzed N-alkylation of amines with alcohols
-
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
-
-
- Recyclable covalent triazine framework-supported iridium catalyst for the N-methylation of amines with methanol in the presence of carbonate
-
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
-
p. 281 - 290
(2021/03/26)
-
- 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)]
-
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
-
p. 2621 - 2631
(2021/02/27)
-
- Ruthenium(ii) complexes with N-heterocyclic carbene-phosphine ligands for theN-alkylation of amines with alcohols
-
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
-
supporting information
p. 3451 - 3461
(2021/05/03)
-
- Additive-freeN-methylation of amines with methanol over supported iridium catalyst
-
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
-
p. 3364 - 3375
(2021/06/06)
-
- Selective N -monomethylation of primary anilines with the controllable installation of N -CH2D, N -CHD2, and N -CD3units
-
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
-
supporting information
p. 4922 - 4926
(2020/07/30)
-
- Catalyst-Free Electrosynthesis of Benzimidazolones through Intramolecular Oxidative C?N Coupling
-
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
-
supporting information
p. 1977 - 1981
(2020/04/20)
-
- Synthesis of: N -methylated amines from acyl azides using methanol
-
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
-
p. 5891 - 5896
(2020/08/21)
-
- EffectiveN-methylation of nitroarenes with methanol catalyzed by a functionalized NHC-based iridium catalyst: a green approach toN-methyl amines
-
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.
-
p. 3458 - 3467
(2020/06/17)
-
- Stereoelectronic and Resonance Effects on the Rate of Ring Opening of N-Cyclopropyl-Based Single Electron Transfer Probes
-
N-Cyclopropyl-N-methylaniline (5) is a poor probe for single electron transfer (SET) because the corresponding radical cation undergoes cyclopropane ring opening with a rate constant of only 4.1 × 104 s-1, too slow to compete with other processes such as radical cation deprotonation. The sluggish rate of ring opening can be attributed to either (i) a resonance effect in which the spin and charge of the radical cation in the ring-closed form is delocalized into the phenyl ring, and/or (ii) the lowest energy conformation of the SET product (5a¢+) does not meet the stereoelectronic requirements for cyclopropane ring opening. To resolve this issue, a new series of N-cyclopropylanilines were designed to lock the cyclopropyl group into the required bisected conformation for ring opening. The results reveal that the rate constant for ring opening of radical cations derived from 1′-methyl-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-quinoline] (6) and 6′-chloro-1′-methyl-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-quinoline] (7) are 3.5 × 102 s-1 and 4.1 × 102 s-1, effectively ruling out the stereoelectronic argument. In contrast, the radical cation derived from 4-chloro-N-methyl-N-(2-phenylcyclopropyl)aniline (8) undergoes cyclopropane ring opening with a rate constant of 1.7 × 108 s-1, demonstrating that loss of the resonance energy associated with the ring-closed form of these N-cyclopropylanilines can be amply compensated by incorporation of a radical-stabilizing phenyl substituent on the cyclopropyl group. Product studies were performed, including a unique application of EC-ESI/MS (Electrochemistry/ElectroSpray Ionization Mass Spectrometry) in the presence of 18O2 and H218O to elucidate the mechanism of ring opening of 7a¢+ and trapping of the resulting distonic radical cation.
- Grimm, Michelle L.,Suleman, N. Kamrudin,Hancock, Amber N.,Spencer, Jared N.,Dudding, Travis,Rowshanpour, Rozhin,Castagnoli, Neal,Tanko, James M.
-
supporting information
p. 2640 - 2652
(2020/02/18)
-
- Methoxycarbonylation of Alkyl-, Cycloalkyl-, and Arylamines with Dimethyl Carbonate in the Presence of Binder-Free Zeolite
-
Abstract: Methyl N-alkyl-, N-cycloalkyl-, and N-arylcarbamates were synthesized by reaction of the correspondingamines with dimethyl carbonate in the presence of binder-free FeHY zeolite. Theoptimal conditions (reactant ratio, amount of the catalyst, temperature,reaction time) were found to afford the target products with high yields.
- Khazipova, A. N.,Khusnutdinov, R. I.,Mayakova, Yu. Yu.,Shchadneva, N. A.
-
p. 1228 - 1235
(2020/10/02)
-
- Bimetallic Bis-NHC-Ir(III) Complex Bearing 2-Arylbenzo[d]oxazolyl Ligand: Synthesis, Catalysis, and Bimetallic Effects
-
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
-
p. 3514 - 3523
(2020/10/09)
-
- Highly Efficient Binuclear Copper-catalyzed Oxidation of N,N-Dimethylanilines with O2
-
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
-
p. 2221 - 2225
(2020/03/23)
-
- 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
-
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
-
supporting information
p. 1835 - 1847
(2020/01/31)
-
- N-Methylation of Amines with Methanol in Aqueous Solution Catalyzed by a Water-Soluble Metal-Ligand Bifunctional Dinuclear Iridium Catalyst
-
The N-methylation of amines with methanol in aqueous solution was proposed and accomplished by using a water-soluble metal-ligand bifunctional dinuclear iridium catalyst. In the presence of [(Cp*IrCl)2(thbpym)][Cl]2 (1 mol %), a range of desirable products were obtained in high yields under environmentally benign conditions. Notably, this research exhibited the potential of transition metal-catalyzed activation of methanol as a C1 source for the construction of the C-N bond in aqueous solution.
- Han, Xingyou,Li, Feng,Liu, Peng,Meng, Chong,Tung, Nguyen Thanh
-
p. 5815 - 5824
(2020/05/26)
-
- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
-
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
-
-
- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
-
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
-
p. 14627 - 14635
(2019/12/02)
-
- 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
-
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
-
p. 6830 - 6839
(2019/06/14)
-
- Catalytic Hydrogenation of Carboxamides with a Bifunctional Cp Ru Catalyst Bearing an Imidazol-2-ylidene with a Protic Aminoethyl Side Chain
-
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
-
p. 2542 - 2547
(2019/06/08)
-
- Binuclear rhodium complex containing ortho-carborane structure and preparation and application thereof
-
The invention relates to a binuclear rhodium complex containing an ortho-carborane structure and preparation and application thereof. The preparation method of the rhodium complex comprises the following steps: 1) adding an n-BuLi solution into an ortho-carborane solution, and then reacting for 30-60 min at room temperature; 2) adding selenium and reacting for 1-2h at room temperature; 3) adding [Cp*RhCl2]2, reacting at room temperature for 3-6h, and performing post-treating to obtain the rhodium complex; and the rhodium complex is used to catalyze arylamine N-methylation reaction to prepare arylamine N-methylated derivatives. Compared with the prior art, the preparation method of the binuclear semi-sandwich rhodium complex containing the ortho-carborane structure is simple and green, has excellent selectivity and higher yield, and the prepared rhodium complex has higher catalytic activity at room temperature, can be used for catalyzing aromatic amine N-methylation reaction to prepare the aromatic amine N-methylation derivatives, has high catalytic reaction yield, and has wide industrial application prospect.
- -
-
Paragraph 0047-0050
(2019/10/01)
-
- 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)
-
- Selective formylation or methylation of amines using carbon dioxide catalysed by a rhodium perimidine-based NHC complex
-
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.
-
supporting information
p. 538 - 549
(2019/02/14)
-
- 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
-
-
- N -Methylation of ortho -substituted aromatic amines with methanol catalyzed by 2-arylbenzo [d] oxazole NHC-Ir(iii) complexes
-
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
-
p. 5072 - 5082
(2019/04/17)
-
- Room temperature N-heterocyclic carbene manganese catalyzed selective N-alkylation of anilines with alcohols
-
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
-
supporting information
p. 6213 - 6216
(2019/06/07)
-
- Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow
-
Selective N-monomethylation of anilines has been achieved under continuous flow conditions using dimethyl carbonate as a green methylating agent in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene. Our methodology takes advantage of the expanded process windows available in the continuous flow regime to safely induce monomethylation in superheated solvents at high pressure. We propose selective N-monomethylation is achieved via an in situ protection-deprotection pathway, which is supported by the observed reactivities of several putative reaction intermediates. The robust and scalable method was applicable to a broad range of primary aniline substrates including ortho-, meta-, and para-substituted anilines, as well as electron-rich and electron-deficient anilines. The synthetic precursor of diazepam, 5-chloro-2-(methylamino)benzophenone, was selectively synthesized under our optimized conditions.
- Seo, Hyowon,Bédard, Anne-Catherine,Chen, Willie P.,Hicklin, Robert W.,Alabugin, Alexander,Jamison, Timothy F.
-
p. 3124 - 3128
(2017/12/11)
-
- 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
-
p. 11813 - 11816
(2018/12/01)
-
- Oxo-bridge bicyclo-[2.2.1]-heptene compound containing boric acid derived group as well as synthesis method and application thereof
-
The invention discloses an oxo-bridge bicyclo-[2.2.1]-heptene compound containing a boric acid derived group as well as a synthesis method and application thereof. A target compound disclosed by the invention is prepared from 3-(4-hydroxylphenyl)-4-(4-boratephenyl)-furan and an ethylene sulfonamide derivative through Diels-Alder reaction and subsequent hydrolysis reaction. The oxo-bridge bicyclo-[2.2.1]-heptene compound has the advantages of relatively high reaction total yield, mild conditions and high speed. An in-vivo experiment proves that compared with an existing breast-cancer-resistingmedicine 4-hydroxytamoxifen (4-OHT), the novel oxo-bridge bicyclo-[2.2.1]-heptene compound containing the boric acid derived group has a higher inhibition effect on proliferation of hormone-dependingbreast cancer MCF-7 cells.
- -
-
-
- Photoinduced Cross-Coupling of Amines with 1,2-Diiodobenzene and Its Application in the Synthesis of Carbazoles
-
A facile and efficient process for the preparation of various tertiary aminobenzenes and carbazole derivatives via photoinduced cross-coupling of amines with 1,2-diiodobenzene is reported. Mechanistic investigations indicate that the transformation proceeds via nucleo-philic addition of an amine to the benzyne intermediate accompanied with a proton transfer process, followed by an oxidative cyclization of the generated diphenylamine to furnish the corresponding carbazole products.
- Zhao, Xinxin,Chen, Ming,Huang, Binbin,Yang, Chao,Gao, Yuan,Xia, Wujiong
-
supporting information
p. 2981 - 2989
(2018/05/15)
-
- Transition-Metal-Free Synthesis of Acridones via Base-Mediated Intramolecular Oxidative C?H Amination
-
Intramolecular oxidative C?H amination of 2-aminobenzophenones was achieved in the presence of potassium tert-butoxide and dimethyl sulfoxide. A series of functionalized acridones were prepared in moderate to excellent yields in a mild, efficient, and transition-metal-free manner. (Figure presented.).
- Wei, Wen-Tao,Sheng, Jian-Fei,Miao, Hui,Luo, Xiang,Song, Xian-Heng,Yan, Ming,Zou, Yong
-
p. 2101 - 2106
(2018/06/14)
-
- 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)
-
- Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach
-
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.
-
p. 6440 - 6445
(2018/07/25)
-
- N-Monomethylation of Aromatic Amines with Methanol via PNHP-Pincer Ru Catalysts
-
The use of methanol for the selective methylation of aromatic amines with RuHCl(CO)(PNHP) (PNHP = bis(2-diphenylphosphinoethyl)amine) is reported. Various aromatic amines were transformed into their corresponding monomethylated secondary amines in high yields at 150 °C with a very low catalyst loading (0.02-0.1 mol %) in the presence of KOtBu (20-60 mol %). The catalyst precursor, RuHCl(CO)(PNHP), was converted to [RuH(CO)2(PNHP)]+ under the catalytic conditions and also serves as a highly effective catalyst. The robustness of this catalyst contributes to its outstanding catalytic activity, even under reaction conditions, in which CO is liberated from methanol.
- Ogata, Osamu,Nara, Hideki,Fujiwhara, Mitsuhiko,Matsumura, Kazuhiko,Kayaki, Yoshihito
-
supporting information
p. 3866 - 3870
(2018/07/25)
-
- Copper-Mediated monochlorination of anilines and nitrogen-containing heterocycles
-
A simple and selective copper(II) chloride-mediated monochlorination of anilines and nitrogen-containing heterocycles has been developed. Stirring a mixture of aniline, copper(II) chloride, lithium chloride in EtOH under reflux condition produced 4-chloroaniline with high yield. Eighteen substrates including substituted anilines, N-substituted anilines, N,N-disubstituted anilines, 5-nitroindole and carbazole were all reactive and afforded desired products in moderate to excellent yields (52%–98%).
- Yang, Xue-Yan,Zhao, Hong-Yi,Mao, Shuai,Zhang, San-Qi
-
supporting information
p. 2708 - 2714
(2018/10/15)
-
- N -Monomethylation of amines using paraformaldehyde and H2
-
The selective N-monomethylation of amines is an important topic in fine chemical synthesis. Herein, for the first time, we described a selective N-monomethylation reaction of amines with paraformaldehyde and H2 in the presence of a CuAlOx catalyst. A variety of amines, including primary aromatic amines, benzylamine and cyclohexylamine, as well as secondary amines, have been shown to be compatible with this reaction.
- Wang, Hongli,Huang, Yongji,Dai, Xingchao,Shi, Feng
-
supporting information
p. 5542 - 5545
(2017/07/06)
-
- Formation of Phenyliodonio-Substituted Spirofurooxindole Trifluoroacetates from N-Substituted 3-Oxopentanediamides via Phenyliodine Bis(trifluoroacetate)-Mediated Oxidative Cascade Reactions
-
The reaction of N-substituted 3-oxopentanediamides with phenyliodine bis(trifluoroacetate) (PIFA) was found to give a novel class of phenyliodonio-substituted spirofurooxindole trifluoroacetates under metal-free conditions. The reaction is postulated to proceed via a cascade process involving an oxidative C—O bond formation, an oxidative C—C bond formation and a final iodination step. (Figure presented.).
- Hu, Bei,Cao, Yang,Zhang, Bobo,Zhang-Negrerie, Daisy,Du, Yunfei
-
supporting information
p. 2542 - 2548
(2017/08/16)
-
- Amide compound and application thereof as TGR5 agonist
-
Belonging to the technical field of medicine, the invention in particular relates to an amide TGR5 agonist compound shown as formula (I), its pharmaceutically acceptable salts, esters, stereoisomers, solvent compounds or prodrugs, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, X, Y, Z, and ring A are defined as the specification. The invention also relates to a preparation method of the compounds, pharmaceutical preparations, pharmaceutical compositions, and application of the compounds in preparation of drugs for treatment and/or prevention of TGR5 activity regulation related diseases. (formula (I)).
- -
-
Paragraph 0274-0276
(2017/04/20)
-
- Tandem Transformation of Nitro Compounds into N-Methylated Amines: Greener Strategy for the Utilization of Methanol as a Methylating Agent
-
A simple air- and moisture-stable, highly efficient ruthenium NNN pincer complex is reported for the first time to catalyze the tandem transformation of various aromatic and aliphatic nitro compounds into the corresponding N-methylated amines in up to 98 % yield by using methanol as a green methylating agent. Gram-scale reactions of challenging nitro substrates demonstrated the practical application aspects of this catalytic system. Importantly, the N-methylamine moiety could be smoothly introduced to various complex molecular structures without using any expensive palladium/phosphine/amine-based cross-coupling reactions.
- Paul, Bhaskar,Shee, Sujan,Chakrabarti, Kaushik,Kundu, Sabuj
-
p. 2370 - 2374
(2017/06/13)
-
- Efficient and selective hydrogenation of amides to alcohols and amines using a well-defined manganese-PNN pincer complex
-
Novel well-defined NNP and PNP manganese pincer complexes have been synthetized and fully characterized. The catalyst Mn-2 containing an imidazolyaminolphosphino ligand shows high activity and selectivity in the hydrogenation of a wide range of secondary and tertiary amides to the corresponding alcohols and amines, under relatively mild conditions. For the first time, more challenging substrates like primary aromatic amides including an actual herbicide can also be hydrogenated using this earth-abundant metal-based pincer catalyst.
- Papa, Veronica,Cabrero-Antonino, Jose R.,Alberico, Elisabetta,Spanneberg, Anke,Junge, Kathrin,Junge, Henrik,Beller, Matthias
-
p. 3576 - 3585
(2017/07/11)
-
- Novel nonmetal catalytic bidirectional selective reduction method of tertiary aromatic amide
-
The invention relates to a novel effective bidirectional selective environment-friendly method for hydrosilation reduction of tertiary aromatic amide and an organic silicon reagent. The method comprises the following steps: selecting a nonmetal catalytic system, and selectively preparing a secondary or tertiary organic amine compound by successively catalyzing tertiary aromatic amide and cheap PHMS or triethoxysilane under a mild condition. By adopting the method, the bidirectional selective reduction of the tertiary aromatic amide is realized by innovatively utilizing an electronic effect and steric hindrance difference of an organic silicon reagent at first time, so that a brand new strategy is provided for the reduction of amide and derivative of the amide, the defects of the traditional method that the substrate functional group is poor in compatibility, the production cost is high and the like can be overcome, and the application prospect of the amine compound prepared in industrial production or laboratory is promising.
- -
-
Paragraph 0026; 0027; 0028; 0029
(2017/10/22)
-