N-methylation Of Amines Research Articles

N-Methylation and Trideuteromethylation of Amines via Magnesium-Catalyzed Reduction of Cyclic and Linear Carbamates.

A new reduction of carbamates to N-methyl amines is presented. The magnesium-catalyzed reduction reaction allows the conversion of cyclic and linear carbamates, including N-Boc protected amines, into the corresponding N-methyl amines and amino alcohols which are of significant interest due to their presence in many biologically active molecules. Furthermore, the reduction can be extended to the formation of N-trideuteromethyl labeled amines.

Catalyst-free selective N-formylation and N-methylation of amines using CO2 as a sustainable C1 source

We herein describe catalyst-free selective N-formylation and N-methylation of amines using CO2 as a sustainable C1 source.

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.

Ultra-small cobalt nanoparticles from molecularly-defined Co-salen complexes for catalytic synthesis of amines.

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions. In the presence of ammonia and hydrogen, cobalt–salen complexes such as cobalt(ii)–N,N′-bis(salicylidene)-1,2-phenylenediamine produce ultra-small (2–4 nm) cobalt-nanoparticles embedded in a carbon–nitrogen framework. The resulting materials constitute stable, reusable and magnetically separable catalysts, which enable the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds and ammonia. The isolated nanoparticles also represent excellent catalysts for the synthesis of primary, secondary as well as tertiary amines including biologically relevant N-methyl amines.

Triazinetriamine-derived porous organic polymer-supported copper nanoparticles (Cu-NPs@TzTa-POP): an efficient catalyst for the synthesis of N-methylated products via CO2 fixation and primary carbamates from alcohols and urea

Copper nanoparticles incorporated triazinetriamine derived porous organic polymer based catalyst was synthesized for catalytic production N-methylated amines and primary carbamates.

Selective N-Formylation and N-Methylation of Amines Using Methanol as a Sustainable C1 Source

Methanol was utilized for C1 functionalization of primary amines; N-formylation, N-methylation, and N,N-formylmethylation. The reactions were achieved via dehydrogenation of methanol with a ruthenium-based catalyst. Various amines were selectively functionalized in moderate to excellent yields (30% to 99%). Mechanistic studies revealed that control of the reversibility between dehydrogenation of the hemiaminal to formamide and hydrogenation of the formamide back to the hemiaminal promotes the selectivity. The hemiaminal intermediate is further dehydrated to an imine, followed by irreversible hydrogenation to generate the N-methyl secondary amine. The N-methyl secondary amine can then undergo formylation to produce N,N-formylmethylamine. It can be also reversibly hydrogenated to the corresponding hemiaminal intermediate. Further dehydration and subsequent hydrogenation can generate N,N-dimethylamine. The hydrogen pressure and reaction temperature are critical to controlling the equilibria and reaction path...

Well-Defined Phosphine-Free Iron-Catalyzed N-Ethylation and N-Methylation of Amines with Ethanol and Methanol.

An iron(0) complex bearing a cyclopentadienone ligand catalyzed N-methylation and N-ethylation of aryl and aliphatic amines with methanol or ethanol in mild and basic conditions through a hydrogen autotransfer borrowing process is reported. A broad range of aromatic and aliphatic amines underwent mono- or dimethylation in high yields. DFT calculations suggest molecular hydrogen acts not only as a reducing agent but also as an additive to displace thermodynamic equilibria.

1,4-Dioxane-Tuned Catalyst-Free Methylation of Amines by CO2 and NaBH4.

A catalyst-free reductive functionalization of CO2 with amines and NaBH4 was developed. The N-methylation of amines was carried out with CO2 as a C1 building block and 1,4-dioxane as the solvent. Notably, the six-electron reduction of CO2 to form the methyl group occurred simultaneously with formation of the C-N bond to give the N-methylated amine.

Direct Synthesis of N,N-Dimethylated and β-Methyl N,N-Dimethylated Amines from Nitriles Using Methanol: Experimental and Computational Studies

Direct and selective synthesis of N,N-dimethylated amines from nitriles using methanol as C1 building blocks is reported using an air- and moisture-stable ruthenium complex. Following this process, various aromatic as well as aliphatic nitriles were converted to the corresponding N-methylated amines. Interestingly, tandem C-methylation as well as N-methylation was achieved by introducing multiple methyl groups. The practical aspect of this process was revealed by preparative-scale reactions with different nitriles and the synthesis of anti-allergic drug “avil”. Several kinetic experiments and detailed DFT calculations were carried out to understand the mechanism of this process.

Copper catalysis: ligand-controlled selective N-methylation or N-formylation of amines with CO2 and phenylsilane

Selective N-formylation or N-methylation of amines was performed by subtly choosing the ligand in copper-promoted reductive functionalization of CO2.

Convenient iron-catalyzed reductive aminations without hydrogen for selective synthesis of N-methylamines

N-Methylated amines play an important role in regulating the biological and pharmaceutical properties of all kinds of life science molecules. In general, this class of compounds is synthesized via reductive amination reactions using high pressure of molecular hydrogen. Thus, on laboratory scale especially in drug discovery, activated (toxic) methyl compounds such as methyl iodide and dimethyl sulfate are still employed, which also generate significant amounts of waste. Therefore, the development of more convenient and operationally simple processes for the synthesis of advanced N-methylamines is highly desired. Herein, we report the synthesis of functionalized and structurally diverse N-methylamines directly from nitroarenes and paraformaldehyde, in which the latter acts as both methylation and reducing agent in the presence of reusable iron oxide catalyst. The general applicability of this protocol is demonstrated by the synthesis of >50 important N-methylamines including highly selective reductive N-methylations of life science molecules and actual drugs, namely hordenine, venlafaxine, imipramine and amitriptyline.

Rhenium-Loaded TiO2 : A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N-Methylation of Amines Using H2 and CO2.

Herein, we report a heterogeneous TiO2 -supported Re catalyst (Re/TiO2 ) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N-methylation of amines, by using H2 and CO2 . Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3-phenylpropionic acid methyl ester to afford 3-phenylpropanol (pH2 =5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N-methylation of amines, and the N-alkylation of amines with carboxylic acids or esters.

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.

N-formylation and N-methylation of amines using metal-free N-heterocyclic carbene catalysts and CO2 as carbon source.

N-formylation and N-methylation of amines are important reactions that are used to produce a wide range of key intermediates and compounds. This protocol describes the environmentally benign N-formylation and N-methylation of primary and secondary amines using carbon dioxide (CO2) as the carbon source, hydrosilanes as reductants and N-heterocyclic carbenes (NHCs) as catalysts. Using CO2 as a reagent has the advantage of low cost and negligible toxicity. However, the catalyst is air-sensitive and must be generated fresh before use; consequently, the techniques used to prepare and manipulate the catalyst are described. The synthetic approach described in this protocol does not use any toxic reagents; using the appropriate catalyst, N-formylated or N-methylated products can be obtained with high selectivity. The overall time for catalyst preparation and for conducting several catalytic reactions in parallel is 15-48 h, depending on the nature of the substrates.

Ionic liquid/H2O-mediated synthesis of mesoporous organic polymers and their application in methylation of amines.

Mesoporous Tröger's base-functionalized polymers (Meso-TBPs) were prepared using a sulfonic acid group functionalized ionic liquid/H2O system, with surface areas up to 431 m2 g-1 and pore sizes of 3-15 nm. Ir(ii) coordinated Meso-TBPs exhibited extraordinary catalytic performance in the N-methylation of amines using methanol.

Glycerol as a Building Block for Prochiral Aminoketone, N-Formamide, and N-Methyl Amine Synthesis.

Prochiral aminoketones are key intermediates for the synthesis of optically active amino alcohols, and glycerol is one of the main biomass-based alcohols available in industry. In this work, glycerol was catalytically activated and purposefully converted with amines to generate highly valuable prochiral aminoketones, as well as N-formamides and N-methyl amines, over CuNiAlOx catalyst. The catalyst structure can be anticipated as nano-Ni species on or in CuAlOx via the formation of nano- Cu-Ni alloy particles. This concept may present a novel and valuable methodology for glycerol utilization.

ChemInform Abstract: N‐Methylation of Amines with Methanol in a Hydrogen Free System on a Combined Al2O3—Mordenite Catalyst.

N-Methyl amines play a major role in the production of medicines, pesticides, surfactants and dyes. N-Methylation of primary or second amines with methanol is considered to be a green path for the synthesis of N-methyl amines and the catalyst is key. In this article, the combined Al2O3–mordenite catalyst (mass fraction of alumina is 40%) with good activity, selectivity, lifetime and stability was prepared for N-methylation of various amines with methanol in a hydrogen free system in a fixed bed reactor, and characterized by XRD, N2 adsorption and NH3-TPD. Furthermore, the methanol adsorption was investigated by in situ FTIR, and the result indicated that methoxyl species may be the active species for the N-methylation of amines.

Pd-Catalyzed N-Methylation of Amines with Paraformaldehyde and Calcium Hydride

Pd-Catalyzed N-Methylation of Amines with Paraformaldehyde and Calcium Hydride

Water as Co-Hydrogen Donor in Reductive Aminations

Reductive amination generates an important reaction in fine chemical synthesis. The employment of water as the hydrogen donor for reductive amination might solve the long-time hydrogen supply problem. Here, we present our new results on reductive N-methylation reactions of amine with paraformaldehyde with water as the co-hydrogen donor catalyzed by a simple supported nanogold catalyst, i.e., Au/Al2O3. N-Methyl amines or N,N-dimethyl amines can be selectively synthesized with excellent yields. Isotope tracing reactions confirmed the transformation of hydrogen from water in the final product. In addition, this method can be applied in the N-methylation reactions of bioactive molecules with excellent performance. This concept may supply a potential methodology for sustainable reductive amination.

N-Methylation of amines with methanol in a hydrogen free system on a combined Al2O3–mordenite catalyst

N-Methylation of primary or second amines with methanol is a green path for the synthesis of N-methyl amines.