- 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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- 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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- 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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- 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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- 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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- 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.
- -
-
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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- Discovery of Potent, Reversible, and Competitive Cruzain Inhibitors with Trypanocidal Activity: A Structure-Based Drug Design Approach
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A virtual screening conducted with nearly 4?000?000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure-activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor (45) exhibited high affinity with a Ki value of 20 nM, presenting both in vitro and in vivo activity against T. cruzi. Furthermore, the most promising compounds reduced parasite burden in vivo and showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for drug discovery efforts.
- De Souza, Mariana L.,De Oliveira Rezende Junior, Celso,Ferreira, Rafaela S.,Espinoza Chávez, Rocio Marisol,Ferreira, Leonardo L. G.,Slafer, Brian W.,Magalh?es, Luma G.,Krogh, Renata,Oliva, Glaucius,Cruz, Fabio Cardoso,Dias, Luiz Carlos,Andricopulo, Adriano D.
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p. 1028 - 1041
(2019/12/27)
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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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- Combined KOH/BEt3Catalyst for Selective Deaminative Hydroboration of Aromatic Carboxamides for Construction of Luminophores
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The selective catalytic C-N bond cleavage of amides into value-added amine products is a desirable but challenging transformation. Molecules containing iminodibenzyl motifs are prevalent in pharmaceutical molecules and functional materials. Here we established a combined KOH/BEt3 catalyst for deaminative hydroboration of acyl-iminodibenzyl derivatives, including nonheterocyclic carboxamides, to the corresponding amines. This novel transition-metal-free methodology was also applied to the construction of Clomipramine and luminophores.
- Li, Jinshan,Wang, Jiali,Yang, Jianguo,Yao, Wubing,Zhong, Aiguo
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supporting information
p. 8086 - 8090
(2020/11/03)
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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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- 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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- Selective mono-N-methylation of nitroarenes with methanol catalyzed by atomically dispersed NHC-Ir solid assemblies
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A series of N-heterocyclic carbene-iridium (NHC-Ir) coordination assemblies based on bis-pyrenoimidazolium salts are prepared, and shown to function as efficient solid molecular catalysts in selective mono-N-methylation of nitroarenes with methanol under mild conditions. The atomically dispersed active Ir(I) centers and the large π-conjugation rings endow the solid catalysts with an exceptionally high activity and selectivity for a broad substrate scope. Such solid NHC-Ir coordination assemblies are robust, which can be easily recovered and reused more than 10 runs without significant loss of their catalytic activity and selectivity. When combined with a subsequent formylation using the same solid catalysts under ambient conditions, this novel protocol can afford diverse formamides in excellent yields, further highlighting the applicability of the present solid catalysts for an efficient diversification of nitroarenes to a broad number of functional amines.
- Chen, Jiangbo,Chen, Zhe-Ning,Tu, Tao,Wang, Jiaquan,Wen, Daheng,Wu, Jiajie,Xu, Xin,Zheng, Qingshu
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p. 337 - 344
(2020/07/03)
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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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- Methoxycarbonylation of Alkyl-, Cycloalkyl-, and Arylamines with Dimethyl Carbonate in the Presence of Binder-Free Zeolite
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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.
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p. 1228 - 1235
(2020/10/02)
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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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- 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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- 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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- Novel spectral manipulations for determinations of Tolnaftate along with related toxic compounds: Drug profiling and a comparative study
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A comparative study using novel quadruple divisor and mean centering of ratio spectra spectrophotometric methods was developed for resolution of five- component mixture of Tolnaftate, β-naphthol (Tolnaftate alkaline degradation product and its toxic impurity), methyl(m-tolyl)carbamic acid (Tolnaftate alkaline degradation product), N-methyl-m-toluidine (Tolnaftate toxic impurity) and methyl paraben (as a preservative). For the novel quadruple divisor method, each component in the quinary mixture was determined by dividing the quinary mixture spectrum by a sum of standard spectrum of equal concentration of the other four components as a quadruple divisor. First derivative of each ratio spectra was then obtained which allowed selective determination of each component without interference from other components in the mixture. The second method was mean centering of ratio spectra that depended on utilizing the mean centered ratio spectra in four successive steps leading to enhancement of the signal to noise ratio. The absorption spectra of the five studied components were recorded in the wavelength range of 210–350 nm. The mean centered fourth ratio spectra amplitudes for each component were used for its determination. The developed methods were successfully applied for determination of laboratory prepared quinary mixtures to ensure method's specificity, then, were further applied on Tinea Cure cream where no interference from excipients. For the first time, Tolnaftate was determined along with its toxic impurity; β-naphthol, that could be absorbed by the skin, causing systemic toxic effects, unlike Tolnaftate that poorly absorbed, indicating the significance of this work. The proposed methods were statistically compared with each other and with the reference method. Furthermore, ICH guidelines were followed for their validation.
- Emam, Raghda A.,Abdelrahman, Maha M.,Abdelaleem, Eglal A.,Ali, Nouruddin W.
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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
-
-
- 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
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p. 14627 - 14635
(2019/12/02)
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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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- Expedient stereospecific Co-catalyzed tandem C-N and C-O bond formation of: N -methylanilines with styrene oxides
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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
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supporting information
p. 11813 - 11816
(2018/12/01)
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- Method for selectively preparing N-monomethylamine compounds by using nitro compound as raw material
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The invention discloses a method for selectively preparing N-monomethylamine compounds by using a nitro compound as a raw material. The method uses the nitro compound as the reaction raw material, formaldehyde as a methylating agent and a hydrogen gas as a reducing agent, in the presence of a supported type catalyst, a reaction is performed for 2-48 h at temperature of 10-180 DEG C in a reaction medium, and therefore the N-monomethylamine compounds are obtained, wherein the catalyst is at least one catalyst supported by palladium, platinum, ruthenium or rhodium. The method disclosed by the invention is simple, and can obtain the target product in a low-cost high-yield and high-selectivity manner; the method simplifies reaction steps, improves reaction efficiency, reduces reaction costs, and avoids separation of an intermediate product primary amine with high toxicity, easy deterioration and difficult storage; the method adopts the H2 as the reducing agent, thereby being clean, inexpensive and environmentally friendly; and the reaction conditions of the method are mild, and the catalyst is non-corrosive and easy to separate and reuse.
- -
-
Paragraph 0035; 0036
(2018/11/03)
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- The design, synthesis and evaluation of selenium-containing 4-anilinoquinazoline hybrids as anticancer agents and a study of their mechanism
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Inhibition of tubulin polymerization is one of the significant strategies in the treatment of cancer. Inspired by the excellent antitumor activity of EP128495 and the beneficial biological activities of selenium compounds, a series of new selenium-containing 4-anilinoquinazoline hybrids were synthesized and evaluated as tubulin polymerization inhibitors. An anti-proliferative activity assay showed that most of the compounds inhibited human sensitive cancer cells at low nanomolar concentrations. A mechanism study revealed that the optimal compound 5a disrupted microtubule dynamics, decreased the mitochondrial membrane potential and arrested HeLa cells in the G2/M phase, finally resulting in cellular apoptosis.
- An, Baijiao,Zhang, Shun,Hu, Jinhui,Pan, Tingting,Huang, Ling,Tang, Johnny Cheuk-On,Li, Xingshu,Chan, Albert S. C.
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p. 4701 - 4714
(2018/07/03)
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- Synthesis and Biological Evaluation of Selenium-Containing 4-Anilinoquinazoline Derivatives as Novel Antimitotic Agents
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Twenty-eight novel selenium-containing 4-anilinoquinazoline derivatives were designed, synthesized, and evaluated as antiproliferative agents. Most of them had significant in vitro activities, particularly for compounds 23a, 25a, and 25d, which also exhibited the most potent antitumor activities against cisplatin-resistant cell lines and the doxorubicin-resistant cell lines, good selectivity toward normal cells, and obvious inhibitory effect on migration of A549 cell lines. Further mechanistic studies revealed that 23a, 25a, and 25d induce G2/M phase arrest and apoptosis in A549 cells, which was associated with a collapse of the mitochondrial membrane potential, alterations in the expression of some cell cycle-related and apoptosis-related proteins, and increasing the intracellular ROS level. Finally, compounds 23a, 25a, and 25d also effectively inhibited the tumor growth in the A549 xenograft model without obvious hints of toxicity. Taken together, these in vitro and in vivo results suggest that 23a, 25a, and 25d may be promising microtubule-stabilizing agents and can be used as a promising lead for the development of new antitumor agents.
- An, Baijiao,Wang, Bo,Hu, Jinhui,Xu, Shaoyu,Huang, Ling,Li, Xingshu,Chan, Albert S. C.
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p. 2571 - 2588
(2018/03/26)
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- Electronic effect of substituents on anilines favors 1,4-addition to: Trans -β-nitrostyrenes: Access to N -substituted 3-arylindoles and 3-arylindoles
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A simple and an efficient method for the regioselective synthesis of N-alkyl/aryl/H 3-arylindole derivatives from N-substituted anilines and trans-β-nitrostyrenes has been described using 10 mol% of bismuth(iii) triflate as a catalyst in acetonitrile at 80 °C. The present protocol profits from the formation of new C-C and C-N bonds, broad substrate scope and moderate to good yields.
- Gattu, Radhakrishna,Bhattacharjee, Suchandra,Mahato, Karuna,Khan, Abu T.
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supporting information
p. 3760 - 3770
(2018/05/30)
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- Highly Selective N-Monomethylanilines Synthesis from Nitroarene and Formaldehyde via Kinetically Excluding of the Thermodynamically Favorable N,N-Dimethylation Reaction
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The synthesis of N-monomethylamine remains a challenging topic because the N,N-dimethylation reaction is thermodynamically favorable. In this work, the kinetically controlled N-monomethylamine synthesis from nitroarene and paraformaldehyde/H2 is reported to have superhigh N-monomethylamine selectivity in the presence of a Pd/TiO2 catalyst. The superior selectivity should be attributed to the preferential adsorption of the primary amine over N-monomethylamine on the Pd/TiO2 surface, as elucidated by NH3/Me2NH-TPD, while the excellent catalytic activity could be associated with the good H2 activation ability and high amine adsorbing capacity of the catalyst, as elucidated by NH3-TPD and H2-TPR tests. Good results were obtained with a variety of nitroarenes containing methyl, methoxyl, hydroxyl, fluoride, trifluoromethyl, ester, and amide substituents as starting materials, and the potential synthetic utility of this protocol in pharmaceutical is illustrated by N-monomethylation of drug molecules, such as clinidipine, nimesulide, procaine, and methyl aminosalicylate.
- Wang, Hongli,Yuan, Hangkong,Yang, Benqun,Dai, Xingchao,Xu, Shan,Shi, Feng
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p. 3943 - 3949
(2018/05/23)
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- Efficient and versatile catalytic systems for the n-methylation of primary amines with methanol catalyzed by n-heterocyclic carbene complexes of iridium
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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
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p. 4617 - 4626
(2019/02/01)
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- Stereospecific copper-catalyzed domino ring opening and sp3 C-H functionalization of activated aziridines with N-alkylanilines
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Copper efficiently catalyzed nucleophilic ring opening, sp3 C-H functionalization, and C-N bond formation in the presence of tert-butyl hydroperoxide to afford functionalized imidazolidines starting from N-sulfonylaziridines and Nalkylanilines. The products were obtained in high optical purities (95 → 99% ee) with excellent functional group tolerance.
- Sengoden, Mani,Bhowmick, Abhisikta,Punniyamurthy, Tharmalingam
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supporting information
p. 158 - 161
(2017/11/27)
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- Method for selectively preparing N-monomethylamine compound
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The invention discloses a method for selectively preparing an N-monomethylamine compound. The method takes an amine compound, formaldehyde and H2 as reaction raw materials; the raw materials react in a reaction medium in the presence of a compound catalyst at 30 DEG C-180 DEG C for 2h-48h, so as to obtain the N-monomethylamine compound; and the compound catalyst is composed of oxides of at least two of the following metal or oxides of least one of the following metal and at least one metal simple substance: aluminum, copper, nickel, cobalt and iron. According to the method for preparing the N-monomethylamine compound, the conversion ratio and the selectivity of N-monomethylamine are relatively high; the H2 is used as a reducing agent and is clean, cheap and environment-friendly; the catalyst utilized by the method is cheap, simple to prepare and high in catalysis efficiency; and the method has mild preparation and reaction conditions and the catalyst has no corrosiveness, is easy to separate and can be repeatedly used.
- -
-
Paragraph 0027; 0032-0033
(2017/08/29)
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- Tandem Transformation of Nitro Compounds into N-Methylated Amines: Greener Strategy for the Utilization of Methanol as a Methylating Agent
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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
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p. 2370 - 2374
(2017/06/13)
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- Novel nonmetal catalytic bidirectional selective reduction method of tertiary aromatic amide
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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.
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Paragraph 0046; 0047; 0048; 0049
(2017/10/22)
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- Rhodium catalyzed regioselective arene homologation of aryl urea via double C–H bond activation and migratory insertion of alkyne
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A convenient rhodium catalyzed oxidative arene homologation of aniline derivatives with symmetrical or unsymmetrical alkynes using Cu(OAc)2as oxidant is described. Urea group is shown to be effective as a directing group for initial ortho C–H activation. Two migratory insertion events of alkyne into Rh–C bond occur successively, both with complete regioselectivity. This method is particularly useful for synthesis of polyarenes with different substituents, which has not been reported with conventional protocol. A mechanism has been proposed to explain the observed data.
- Wang, Yan,Zhou, Hao,Xu, Ke,Shen, Mei-Hua,Xu, Hua-Dong
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supporting information
p. 92 - 96
(2017/01/12)
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- Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into γ-amino- N -Boc-enamines
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Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into γ-amino-N-Boc-enamines was demonstrated. The scope and limitation, experimental mechanistic studies, and a proposed reaction mechanism were also described.
- Tayama, Eiji,Kobayashi, Yoshiaki,Toma, Yuka
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p. 10570 - 10573
(2016/09/02)
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- Pd(II)/Ag(I)-Promoted One-Pot Synthesis of Cyclic Ureas from (Hetero)Aromatic Amines and Isocyanates
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A simple and facile one-pot reaction has been developed to afford a diverse range of N,N′-disubstituted benzimidazolones and imidazopyridinones containing two differently substituted N atoms. A cooperative Pd(II)/Ag(I) system promotes the sequential addition/intramolecular C-H amidation reaction of (hetero)aromatic amines and isocyanates, leading to the formation of two C-N bonds. A mechanism involving radical intermediates generated by single-electron transfer (SET) in the presence of a Ag2CO3 oxidant and Pd(OAc)2 Lewis acid is proposed. This protocol offers an operationally easy, simple, and robust approach with the use of readily available starting materials, good functional group tolerance, and high efficiency.
- Youn, So Won,Kim, Yi Hyun
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p. 6140 - 6143
(2016/12/09)
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- Methylation of aniline and its derivatives with dimethyl carbonate in the presence of binder-free micro-, meso-, and macroporous zeolites KNaX, NaY, and HY
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Aniline and its derivatives undergo methylation when treated with dimethyl carbonate in the presence of binder-free micro-, meso-, and macroporous zeolites KNaX, NaY, and HY leading to the formation of N-methyl- and N,N-dimethylanilines.
- Khusnutdinov,Shchadneva,Mayakova, Yu. Yu.,Ardieva,Khazipova,Kutepov
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p. 1565 - 1570
(2017/01/28)
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- Iron-catalysed sequential reaction towards α-aminonitriles from secondary amines, primary alcohols and trimethylsilyl cyanide
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We have developed a one-pot iron-catalysed sequential reaction of secondary amines with primary alcohols, trimethylsilyl cyanide and TBHP under mild reaction conditions to give the corresponding α-aminonitriles.
- Shen, Hang,Hu, Liangzhen,Liu, Qing,Hussain, Muhammad Ijaz,Pan, Jing,Huang, Mingming,Xiong, Yan
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supporting information
p. 2776 - 2779
(2016/02/19)
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- Room-temperature copper-catalyzed arylation of dimethylamine and methylamine in neat water
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The first room-temperature copper-catalyzed arylations of dimethylamine and methylamine in neat water have been developed. Using a combination of CuI and 6,7-dihydroquinolin-8(5 H)-one oxime as catalyst, dimethylamine is arylated with various aryl halides to give the corresponding products in good to excellent yields. Further, this catalysis enables the selective arylation of methylamine to afford the high yields of monoarylated methylamines as the sole products.
- Wang, Deping,Kuang, Daizhi,Zhang, Fuxing,Yang, Chunlin,Zhu, Xiaoming
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supporting information
p. 714 - 718
(2015/03/18)
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- Palladium-catalyzed oxidative carbonylation of aromatic C-H bonds of N -alkylanilines with CO and alcohols for the synthesis of o -aminobenzoates
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A Pd(II)-catalyzed C-H monocarbonylation of N-alkylanilines for the synthesis of o-aminobenzoates has been developed. Various aliphatic alcohols and phenol were tolerated in the reaction to afford the corresponding o-aminobenzoates in good yields under mild balloon pressure of CO.
- Chen, Ming,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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p. 1258 - 1263
(2015/01/30)
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- Copper(II)-catalyzed oxidative N-nitrosation of secondary and tertiary amines with nitromethane under an oxygen atmosphere
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The combination of a catalytic amount of Cu(OTf)2 and less than a stoichiometric amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under an O2 atmosphere effectively promoted the N-nitrosation of both secondary aromatic/aliphatic amines and tertiary aromatic amines with nitromethane (CH3NO2) leading to the preparation of N-nitrosamine derivatives.
- Sakai, Norio,Sasaki, Minoru,Ogiwara, Yohei
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supporting information
p. 11638 - 11641
(2015/07/15)
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- A 2,6-bis(phenylamino)pyridinato titanium catalyst for the highly regioselective hydroaminoalkylation of styrenes and 1,3-butadienes
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The C-C bond forming catalytic hydroaminoalkylation of terminal alkenes, 1,3-dienes, or styrenes allows a direct and highly atom efficient (100 %) synthesis of amines which can result in the formation of two regioisomers, the linear and the branched product. We present a new titanium catalyst with 2,6-bis(phenylamino)pyridinato ligands for intermolecular hydroaminoalkylation reactions of styrenes and 1-phenyl-1,3-butadienes that delivers the corresponding linear hydroaminoalkylation products with excellent regioselectivities. Linear progress: A new Ti complex with 2,6-bis(phenylamino) pyridinato ligands catalyzes highly regioselective hydroaminoalkylation reactions of styrenes. The process that directly gives access to the corresponding linear hydroaminoalkylation products offers a new and flexible synthetic approach towards pharmaceutically important 3-arylpropylamines. It is also possible to convert (E)-1-phenyl-1,3-butadienes into the corresponding linear products.
- Doerfler, Jaika,Preuss, Till,Schischko, Alexandra,Schmidtmann, Marc,Doye, Sven
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p. 7918 - 7922
(2014/08/05)
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- N-Methylation of amine and nitro compounds with CO2/H2 catalyzed by Pd/CuZrOx under mild reaction conditions
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An active Pd/ZrCuOx catalyst was prepared for the reductive amination of CO2. The N-methylation of amines and nitro compounds with CO2/H2 can be realized with up to 97% yield under relatively mild reaction condi
- Cui, Xinjiang,Zhang, Yan,Deng, Youquan,Shi, Feng
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supporting information
p. 13521 - 13524
(2015/01/09)
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- A facile protocol for the synthesis of mono-N-methyl anilines via formimidate intermediates
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A general procedure for the preparation of mono-N-methyl anilines has been developed with excellent yields. This protocol relies on a NaBH3(OAc) reduction of formimidate intermediates that are quantitatively generated by treatment of primary substituted anilines with triethyl orthoformate under the catalysis of MCM-41-SO3H mesoporous zeolite. The newly developed procedure was facile, efficient, and environmentally benign.
- Sun, Nan,Wang, Shuai,Mo, Weimin,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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experimental part
p. 7142 - 7148
(2010/09/14)
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- Selective monomethylation of anilines by Cu(OAc)2-promoted cross-coupling with MeB(OH)2
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N-Methylanilines are readily synthesized in high yields through the copper(ll)-promoted coupling of anilines and methylboronic acid. This method represents a new approach for the selective monomethylation of anilines, and it is the first reported example
- Gonzalez, Israel,Mosquera, Jesus,Guerrero, Cesar,Rodriguez, Ramon,Cruces, Jacobo
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supporting information; experimental part
p. 1677 - 1680
(2009/09/06)
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- Highly specific N-monomethylation of primary aromatic amines
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A synthetic methodology for the specific conversion of primary aromatic amines into their N-monomethyl derivatives under very mild conditions is presented. Anilines are treated with 4-nitrobenzenesulfonyl (nosyl) chloride to generate the corresponding sulfonamides 2 in high yields. The subsequent N-methylation reaction of the sulfonamides 2 with a solution of diazomethane is rapid and quantitative. Removal of the nosyl protecting group is readily carried out using the reagent system mercaptoacetic acid/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording the N-monomethylated aromatic amines 4. The procedure is convenient, efficient, and gives rise to the N-monomethyl-anilines exclusively.
- Le Pera, Adolfo,Leggio, Antonella,Liguori, Angelo
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p. 6100 - 6106
(2007/10/03)
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- Investigations of Steric and Electronic Factors Influencing the Cyclopalladation of meta-Toluidine Analogues
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The cyclopalladation of two different types of aniline derivatives is described: the acetylated anilines N-(3-methylphenyl)acetamide (2a), 3-(acetylamino)-4-chlorobenzoic acid (2c), and N-(2-chlorophenyl)acetamide (2d) are cyclometalated easily with palladium(II) acetate and trifluoroacetic acid to yield the corresponding complexes 4a, 4c, and 4d, respectively, whereas the acetylated meta-toluidine N-(2-chloro-5-methylphenyl)acetamide (2b) cannot be metalated at the only accessible site between the acetylamino and the methyl group.This aromatic C-H bond can be activated, however, with the second type of meta-toluidine derivatives: the 2-chloro-5,N-dimethyl-N-nitrosoaniline (3b) readily undergoes cyclopalladation to yield the corresponding Pd(II) complex di-μ-trifluoroacetato-bisdipalladium(II) (5b) containing a five-membered palladacylce with coordination of Pd(II) at the nitroso N-atom, which is established by 15N-NMR spectroscopy.
- Mossi, Waldo,Klaus, Alfred J.,Rys, Paul
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p. 2531 - 2537
(2007/10/02)
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- Reactions of Carbonyl Compounds in Basic Solutions. Part 14. The Alkaline Hydrolysis of Substituted N-Methylformanilides, N-Methylacetanilides, 1- Phenylazetidin-2-ones, 1-Phenyl-2-pyrrolidones, and 1-Phenyl-2-piperidones
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The rate coefficients for the alkaline hydrolysis of a series of substituted 1-phenylazetidin-2-ones, -2-pyrrolidones, and -2-piperidones, and N-methylacetanilides and N-methylformanilides in aqueous dimethyl sulphoxide and in aqueous dioxane or water have been measured at several temperatures.The reactions were first order in substrate and, for the lactams and acetanilides, first order in base and, for the formanilides, both first and second order in base.Hammet reaction constants and activation parameters have been evaluated for each system.The relative reactivity,salt, solvent and solvent isotope effects have been examined.The following mechanisms for the reactions are suggested.For the β-lactams, the bathway appears to be the rate determining attack by hydroxide and, for the γ- and δ-lactams and acetanilides, rate determining fission of the carbon-nitrogen link, which follows equilibrium addition of the base.The formanilides appear to form a tetrahedral intermediate with hydroxide which can collapse to product via rate-determining water- or base- catalysis.
- Bowden, Keith,Bromley, Keith
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p. 2103 - 2109
(2007/10/02)
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- Enamine Rearangement of Pyridinium Salts: Part VIII - Effect of Nucleophilic Reagent on Pyridinium Salts
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N-Methoxy-2-methyl-(IIa) and N-methoxy-2,6-dimethyl-pyridinium salts (IIb) undergo ring opening and recyclization reactions when heated with methylammonium silphite to give N-methyl-aniline (IVa) and N-methyl-m-toluidine (IVb), respectively.
- Fadda, A. A.,Khalil, A. M.,Elmorsy, S. S.,El-Habbal, M. M.
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p. 266 - 268
(2007/10/02)
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- KINETICS AND MECHANISM OF ACID CATALYZED DECOMPOSITION OF SUBSTITUTED 1,3-DIPHENYLTRIAZENES
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The kinetics of acid catalyzed decomposition of 3-substituted and 1,3-disubstituted 1,3-diphenyl-3-methyltriazenes have been studied in 40percent aqueous ethanolic buffers at 25 deg C.The reaction constant for substitution of the phenyl ring at the 3 position of the triazene chain has been determined and the reaction constants of the protonation and bond splitting between the nitrogen atoms 2 and 3 have been estimated.By the covariance analysis it has been found that the standard constants of the Hammett relation are better than the constants determined in the media of organic solvents.Also estimated were the values of the slope β1g of the linear relation between the rate constants and the equilibrium between the diazonium salt and diazotate.The A-SE2 mechanism is suggested as probable, the bond between nitrogen atoms of triazene chain being more than half split in the transition state and the nitrogen-proton bond formation being more advanced than the nitrogen-nitrogen bond splitting.
- Svoboda, Petr,Pytela, Oldrich,Vecera, Miroslav
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p. 2217 - 2224
(2007/10/02)
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