key: cord-0883741-6ms3vpks
authors: Liu, Jianguo; Song, Yanpei; Wu, Xiang; Ma, Longlong
title: N-Dimethylation and N-Functionalization of Amines Using Ru Nanoparticle Catalysts and Formaldehyde or Functional Aldehydes as the Carbon Source
date: 2021-08-26
journal: ACS Omega
DOI: 10.1021/acsomega.1c01961
sha: d0a7d198a887b6aae3a085ff6102dce773f405ae
doc_id: 883741
cord_uid: 6ms3vpks

[Image: see text] N-methylated amines are essential bioactive compounds and have been widely used in the fine and bulk chemical industries, as well as in pharmaceuticals, agrochemicals, and dyes. Developing green, efficient, and low-cost catalysts for methylation of amines by using efficient and easily accessible methylating reagents is highly desired yet remains a significant challenge. Herein, we report the selective N-dimethylation of different functional amines with different functional aldehydes under easy-to-handle and industrially applicable conditions using carbon-supported Ru nanoparticles (Ru/C) as a heterogeneous catalyst. A broad spectrum of amines could be efficiently converted to their corresponding N,N-dimethyl amines with good compatibility of various functional groups. This method is widely applicable to N-dimethylation of primary amines including aromatic, aliphatic amines with formaldehyde, and synthesis of tertiary amines from primary, secondary amines with different functional aldehydes. The advantage of this newly described method includes operational simplicity, high turnover number, the ready availability of the catalyst, and good functional group compatibility. This Ru/C catalyzed N-dimethylation reaction possibly proceeds through a two-step N-methylation reaction process.

N-Functionalized amines, especially N-methyl amines and form-amides, are very important intermediates and building blocks as they are widely used in the synthesis of dyes, perfumes, pesticides, and pharmaceutical products. 1 Nmethylated compounds generally prepared from the Nmethylation method, which is an efficient and powerful method for regulating the biological and pharmaceutical properties by incorporating into a magic methyl group, are also prevalent in naturally occurring and synthetic biologically active compounds. 1d2 As reported by Njarqarson and coworkers in the top 200 Small Molecule Pharmaceuticals by Retail Sales in 2018, there were more than 25 of the top 200 prescribed pharmaceutical products containing N-monomethyl or N-dimethyl groups. 3 Specifically, since the global pandemic of novel corona-virus disease 2019 caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) widely spread worldwide, N-methylated functional drugs especially azithromycin showed to be highly effective in the control of COVID-19 infection (Figure 1 ). 4 Since methyl-substituted amines exist frequently as bioactive compounds and pharmaceutical drugs, the development of more efficient, green, economical, and sustainable methylation processes continuously attracted the attention of chemists in the last few decades. 1d,2a,e,5 Until then, several methodologies for the synthesis of N-methylamines have been developed and widely used in academics and industry. The traditional methodologies for N-methylation typically employ the methylation of amines with activated methyl compounds, such as toxic methyl iodide, 6 dimethyl sulfoxide, 2d7 or dimethyl carbonate. 8 These processes have serious issues that are operationally problematic and generally suffer from narrow scopes of amines and generation of byproducts and a large amount of waste. Transition-metal-catalyzed methylation of amines has become an efficient, practical, and cost-effective method for the one-pot selective synthesis of N-methylamines with C 1 sources. 1d,2a−c,5h,j,l,9 In recent years, with the environmental problem issues and the green, sustainable chemistry, the C 1 sources used in transition-metal-catalyzed N-methylation of amines have predominantly more environmentally benign and safer methylation reagents, such as MeOH, 5j 10 CO 2 , 1d, e, 2c, 5e, f , l, 9i, 11 HCOOH, 12 (para)formaldehyde, 9f1314 and so on (Figure 2a, b) . Until now, various homogeneous and heterogeneous metal catalysts have been reported.

As for the homogeneous catalyst system, Ru complex catalysts have been widely used and studied for the direct Nmethylation of amines using CO 2 as a C 1 source. In 2013, Beller and co-workers did pioneer work on the combination of homogeneous catalyst systems, applying commercially available RuCl 2 (dmso) 4 and BuPAd 2 ligands for the general 

http://pubs.acs.org/journal/acsodf Article methylation of amines using PhSiH 3 and CO 2. 1d Many aromatic and aliphatic, secondary, and primary amines with various functional groups were well tolerated under the optimized reaction conditions (30 bar CO 2 , 4 equiv PhSiH 3 , toluene, 100°C, and 16 h). In the meantime, they also demonstrated highly selective N-methylation of amines using an in situ combination of commercially available Ru (acac) 3 , triphos, and acid or LiCl additives. 2c Various kinds of monomethylation and dimethylation products were obtained in good to excellent yields under the optimized reaction conditions (20 atm CO 2 , 60 atm H 2 , THF, 140°C, 24 h). Later, Klankermayer and co-workers also found that the readily commercially available Ru (triphos)(tmm) complex and the HNTf 2 acid served as a highly efficient homogeneous catalyst system for catalytic reductive N-methylation of imines using CO 2 and H 2 . 2e Some tertiary N-methyl amines were produced with moderate to excellent yields in the three-component coupling reaction of primary amines, aldehydes, and CO 2 . From then on, not only various homogeneous Ru-catalyzed Nmethylation systems [RuCp*Cl 2 ] 2 /dpePhos 10a and [Ru(pcymene)I 2 ] 2 13b but also other transition-metal homogeneous catalyst systems such as Fe, 5m,9h,15 Karstedt's complex, 8b16 Ir, 5j17 Rh, 5n Cu, 5l,9d,12c Co, 10c and Mn 5h,9g,18 have been successively developed.

It is known that homogeneous catalysts normally suffer from several disadvantages such as difficult separation of the catalyst/product, the necessity for additives (ligands, acids, and salts), and difficulty to reuse. As such, from both economic and environmental perspectives, effective heterogeneous catalysis has also been developed and widely used in transition-metal-catalyzed N-methylation reactions. In 1951, Pearson and Bruton reported the reductive methylation of amines with the pre-reduced Adams catalyst Pt using H 2 and HCHO. 19 79% yield of N,N-dimethylglycine was obtained from the reductive methylation of glycine. Half a decade later, in 2009, Li and co-workers 20 described pretreated Raney Nicatalyzed N-methylation of nitroarenes with methanol under 170°C and 3 MPa Ar. Methanol served as a hydrogen source, alkylating reagent, and solvent simultaneously. Several years later, Rong and co-workers 21 reported the one-pot synthesis of N,N-dimethyl anilines with HCHO and nitroarenes catalyzed by the quenched skeletal Cu catalyst. Many N,N-dimethyl aniline products were obtained in good to excellent selectivity under the optimized reaction condition (nitroarenes: 6 mmol, HCHO: 18 mmol, 0.5 g skeletal Cu catalyst, 13 bar H 2 , 70− 100°C, 37−127 min). Recently, Shi and co-workers 5c,9a found that two simple heterogeneous catalysts CuAlO x and Pd/ CuZrO x , which showed high reactivity and selectivity for the transformation of primary and secondary amines as well as nitro compounds into N-methyl or N,N-dimethyl products with CO 2 and H 2 (reaction conditions: 30−100 bar, 150−170°C , 30−48 h). They also developed the efficient TiO 2supported nano-Pd catalyzed N-methylation of nitro compounds with MeOH under UV irradiation at room temperature. 22 In 2015, Cao and co-workers 23 reported the first heterogeneous Au/rutile catalyst for the one-pot N-methylation of nitroarenes. A variety of amines including aromatic, aliphatic, secondary, and primary amines were converted smoothly to the corresponding methylation products with good to excellent yields under the optimized reaction conditions (2 MPa CO 2 , 6 MPa H 2 , 140−170°C, 7 h). Recently, much more efficient transition-metal heterogeneous catalyst systems such as Pt-MoOx/TiO 2 , 9b Au/Al 2 O 3 , 23 PdZn/ TiO 2 , 9i and Pd/TiO 2 , 24 have been successively developed. Specifically, inexpensive copper-9f and cobalt-based 25 ( Figure  2c ) heterogeneous catalysts are found to be good alternatives of palladium-base catalysts or iron-, nickel-, copper-, and cobalt-based homogeneous catalysts with toxic ligands in recent years. In 2019, Yang and co-workers 9f developed an inexpensive heterogeneous Cu nanoparticle catalyst derived from CuAl-layered double hydroxide via an in situ topotactic transformation process. The heterogeneous catalyst Cu/Al 2 O 3 demonstrated excellent efficiency for one-pot reductive Nmethylation of easily available nitroarenes with para-formaldehyde with good compatibility of various functional groups under the optimized reaction conditions (nitroarenes: 0.5 mmol, Cu/Al 2 O 3 12 mg, 27 mol % Cu, 15 equiv (CH 2 O) n , 2 equiv Na 2 CO 3 , 130°C). So far, the state of reported works has one or several of the following issues: transition-metal-based homogeneous catalysts generally need complex or even toxic ligands and also tedious product separation processes; earthabundant transition-metal-based heterogeneous catalyzed Nmethylation usually was carried out under harsh conditions; a high equivalent of base and/or reducing agents was required in many of the homogeneous and heterogeneous catalyst systems.

To overcome these problems, specifically in the sustainable and environmental perspective, several factors are required for developing a new methodology of N-methylamines, including the use of a cheap, green reagent and green byproduct generation (in general, H 2 O) or a fully atom-economic process without any byproduct formation; fairly cheap and industrially scalable heterogeneous catalysts; and mild conditions, easy and convenient procedures of product separation, and downstream processing.

Recently, we found that the graphene sphere-encapsulated uniform Ni/NiO nanoalloy catalysts Ni/NiO@C were efficient in the reductive amination of carbonyl compounds. 26 Surprisingly, several N,N dimethylation products were obtained in excellent yield using aromatic amines and formaldehyde. In the meantime, we also found that the commercially available Ru/C showed excellent reactivity and selectivity for N,N-dimethyl benzylamine. To the best of our knowledge, commercially available Ru/C has remained unexplored for N-methylation of aromatic amines using inexpensive, readily available formaldehyde as a C 1 source and a H 2 source. This Ru/C has a lot of benefits such as the following:

(1) it is air-stable, easy to handle, and readily available; (2) it shows excellent catalytic activity in the absence of a ligand and base; (3) it can be easily separated from the reaction medium by simple filtration; and (4) the only byproduct is H 2 O. Inspired by the abovementioned developments on Nmethylation and based on the attractive catalytic features of Ru/C, we describe here an efficient N-methylation reaction utilizing different functional aldehydes and amines. Using this commercially available heterogeneous catalyst and starting from inexpensive, readily available aldehydes, primary and secondary amines, and molecular hydrogen, we undertook the synthesis of >50 functionalized, structurally diverse linear and branched benzylic and aliphatic N-methylation products.

The reaction was conducted in a stainless steel autoclave (Anhui Kemi Machinery Technology Co., Ltd., China) with six wells (10 mL per well), one thermocouple, and one set of circulating water cooling equipment. Each well has a glass lining and loaded with one 10 mm magnetic stirring bar, 0.5 mmol of the corresponding amine, 3 mmol of the corresponding aldehyde, 0.05 mmol of 1,3,5-trimethoxybenzene, 10 mg of catalyst, and 5 mL of methanol. Then, the autoclave was sealed and purged with H 2 three times at 2.5 MPa pressure and was pressurized with 2.5 MPa H 2 . The autoclave was placed into a heating mantle, and the stirring rate was set at 300 rpm. The autoclave was preheated from room temperature to the target temperature (inside temperature detected by the thermocouple) at a rate of 2°C·min −1 . The target temperature was used as the reaction temperature. The reaction was proceeding at the reaction temperature for the required time. After the reaction, the remaining gas was discharged after the autoclave was cooled down to room temperature. The reaction solutions were collected with a dropper and filtered. The catalyst was immobilized on a magnetic stirring bar and washed thoroughly with ethanol and water. The catalyst (together with a magnetic stirring bar) was then dried at −48°C for 12 h in vacuum by using a freeze dryer.

The reaction products were identified by GC−MS and 1 H NMR, and the yields of reaction products were determined by GC with 1,3,5-trimethoxybenzene as the internal standard. For 1 H NMR analysis, about 2 mL of reaction solutions was concentrated by rotary evaporation, and then 0.5 mL of CDCl 3 was added (preneutralized with basic Al 2 O 3 ).

The source of the chemicals, specific reaction steps, analysis methods, etc. are described in detail in the Supporting Information.

The scanning electron microscopy (SEM) images for the Ru/ C sample (Figure 3a) showed small catalyst particles. Elemental analysis indicated that the catalyst consisted of 5.5 wt % Ru. The TEM measurements were performed to investigate the morphology and distribution of Ru species in Figure 3 . Characterization of Ru/C. SEM images of 5% Ru/C (a), EDS elemental analysis of 5% Ru/C (b), HRTEM images of 5% Ru/C (c and d), N 2 adsorption and desorption isotherm curves and pore size distribution profile of 5% Ru/C (e), and XRD images of 5% Ru/C (f). the catalyst Ru/C. It was observed that Ru NPs with an average size of 10 nm are non-uniformly dispersed on carbon and some Ru nanoparticles were agglomerated at some parts ( Figure 3c ). The nitrogen physisorption measurements for the Ru/C catalyst in the specific surface area (Brunauer−Emmett− Teller method) were following the SEM phenomenon. The Ru/C catalyst has quite a large surface area with 1061.8 m 2 g −1 with an almost identical pore size distribution (>95% micropores with a total pore volume of 0.498 cm 3 g −1 and average pore width of 1.87 nm) (Figure 3e ). The XRD spectra showed that the graphitic carbon shell and the Ru nanoparticles phases are present in the Ru/C sample (Figure 3f ). The weak and broad C (002) peak also confirm that thin graphene shells have been formed, which agrees with the statistical analysis of layers in TEM (Figure 3d ). For the Ru/C catalyst containing a small amount of Ru species, a diffraction peak was observed at about 44.3°corresponding to the Ru (111) plane.

Initially, heterogeneous transition-metal-catalyzed N-methylation was evaluated using benzylamine and formaldehyde. In the beginning, we investigated different reaction temperatures of Ru/C catalyzed N-methylation and it turns out that the Nmethylation can be carried out in excellent selectivity under a fairly mild reaction temperature of 70°C. Further optimization showed that Ru/C catalyzed benzylamine smoothly to the corresponding N-dimethyl products in 8 h. As shown in Table  1 , the hydrogen pressure had a great effect on the production of N-dimethyl products (entry 8−12). Interestingly, unlike previously reported processes, 27,28 the commercially available Pt/C, Raney-nickel, and Raney-cobalt as well as Pd/C showed excellent reactivity and selectivity of >99% yield of N-dimethyl product 1. NiO, iron powder, and zinc were not active in the methylation of benzylamine under the chosen conditions.

After having a convenient protocol in hand for the benchmark reaction, we explored the substrate scopes of Ru/ C-catalyzed N-methylation of different functional primary amines with formaldehyde (Table 2) . At first, 15 kinds of aromatic, heterocyclic, and aliphatic amines having different functional groups were converted to the corresponding N,Ndimethylamines in good to excellent yields using Ru/C. The strong electron-donating group −OMe in the para position has little effect on the catalytic reactivity and N,N-dimethylamine product 2 selectivity. The aromatic amine with an aliphatic chain was transformed to the corresponding dimethylation product 3 with excellent yield (96%). The meta-halosubstituted aromatic amine was also tolerated in this reaction and can be transformed to the meta-halo-substituted N,Ndimethylamine product 4 in excellent yield. The substrate having a weak electron-donating group −Me in the para position had a lower yield of 83% for the dimethylation product 5 compared with the one having a strong electrondonating group −OMe. Interestingly, the N,N-dimethylaniline 6 and N 1 ,N 1 ,N 4 ,N 4 -tetramethylbenzene-1,4-diamine 7 could also be obtained in good yields of 70 and 62%, respectively. Probably due to the steric effect, the ortho-halo-substituted N,N-dimethylamines product 8 was only obtained in 54% yield. Interestingly, the biomass derivative reductive amination product cyclopenta-1,3-dienylmethanamine, prepared from the previous report process, 26 could also give the desired product 10 in 68% yield. Linear and branched aliphatic N,Ndimethylated products, which were previously seldom reported and some with low yield, 5c2329 were obtained in excellent yield under the optimized mild reaction conditions. The commercially available Pt/C, which showed an excellent capacity of catalyzing N-methylation of anilines and aromatic imines with formic acid in the presence of PhSiH 3 under 80°C after 15 h, 12b was also investigated under the present optimized Reaction conditions: 10 mg of catalyst, 5% Ru/C catalyst, 0.5 mmol of benzylamine, 3 mmol of formaldehyde, 5 mL of methanol. Yields and conversion were determined by GC using 1,3,5-trimethoxybenzenen as an internal standard. reaction conditions using green reducing reagent H 2 . Notably, the presence of electron-donating or electron-withdrawing groups in the para position of the aromatic ring did not have a significant influence on the product yield (17 and 20). Nevertheless, the meta chloro-substrate was also well tolerated under the same reaction conditions (19) . The commercially available Raney Ni and Raney Co catalysts were also investigated in this N-methylation reaction (22−33) . Excellent yields were obtained for most of the tested substrates except for the meta chloro-substrate using Raney Ni as a catalyst.

Encouraged by the success in the synthesis of tertiary amine by N-methylation of primary amine catalyzed by Ru/C with formaldehyde, we then explored the synthesis of tertiary amine starting with secondary amine with formaldehyde or primary and secondary amines with different functional groupsubstituted aldehydes, which were seldom reported previously. (Table 3 ) To our delight, the non-substituted and halosubstituted aromatic secondary amines, N-methyl(phenyl)methanamine, and aliphatic amines were converted to the corresponding tertiary amines with excellent yields using formaldehyde (34−40). Tertiary amines with different func-tional groups are important building blocks in bioactive molecule synthesis and materials application. In this context, we applied the Ru/C-catalyzed N-methylation methodology to synthesize tertiary amines using primary and secondary amines with different functional group-substituted aldehydes. Primary amines can react with benzaldehyde, halo-substituted benzaldehyde, and aliphatic aldehydes to give the tertiary amines in moderate to excellent yields (41−45). To the best of our knowledge, very limited work illustrated the synthesis of tertiary amines starting with secondary amines and functional aldehydes using the transition-metal catalyst N-methylation method. Notably, the Ru/C catalyst also showed excellent activity in the N-alkylation of secondary amines with aromatic, para-substituted aromatic aldehydes as well as linear and cyclic aliphatic aldehydes (46−50) . Meanwhile, we also tested the catalyst's reusability, and after three recycle tests, the yield of 1 was dropped from 99 to 60% due to the leaching of the transition metal. Thus, we are still focusing on designing and preparing more suitable catalyst supports, like grapheneencapsulated transition-metal catalysts, which were reported Table 2 . Synthesis of Tertiary Amines by Transition-Metal-Catalyzed N-Methylation of Primary Amine a a Reaction conditions: 10 mg of catalyst, 5% Ru/C catalyst, 5% Pt/C catalyst, 0.5 mmol of amine substrate, 3 mmol of formaldehyde, 5 mL of methanol. Yields and conversion were determined by GC using 1,3,5-trimethoxybenzenen as an internal standard. previously by our group, to avoid metal leaching and enhance the catalytic activity and reusability.

Mechanism Study. Based on the scope studies and the results from the control experiments, unlike the previously reported N-methylation process using the formaldehyde− formic acid process, CO 2 was not observed in this process. Thus, a possible proposed mechanism of Ru/C-catalyzed Nmethylation of phenylmethanamine with formaldehyde is similar to the reported two-step N-methylation process, 9f27 As depicted in Figure 4 , first, phenylmethanamine reacted with one molecule of formaldehyde to form the intermediate (benzylamino) methanol then followed by a dehydration reaction to give the imine, enamines, or iminium ions. In the meantime, the H−H bond is activated on the surface of Ru/C, and the imine intermediate is also absorbed on Ru/C. Then, the imine was reduced by H−H to form N-methyl(phenyl)methanamine. Surprisingly, the aliphatic amines also showed excellent reactivity in this Ru/C N-methylation reaction. They were unreactive in the previous reported Pt/C N-methylation reaction, probably due to the weak adsorption on Pt/C, which was caused by the lack of aromatic π−Pt interaction. 12b In the second step of N-methylation of N-methyl(phenyl)-methanamine, it is slightly different from the first one. N-Methyl-N-methylene(phenyl)methanaminium is more stable in the alkaline aqueous after dehydration. Reduction of the iminium intermediate with H 2 and desorption deliver the Nmethylation product N,N-dimethyl (phenyl) methanamine.

In conclusion, we have demonstrated a simple, practical, and highly efficient ruthenium heterogeneous catalyst for the Nmethylation of a variety of amines with different functional aldehydes under mild conditions. Both primary and secondary amines with various functional groups including aromatic, aliphatic, halo-substituted, furan, and thiophene substituents can be methylated in the presence of formaldehyde at a temperature of 70°C. Importantly, a variety of tertiary amines were synthesized in excellent yield up to 96% by Ru/Ccatalyzed N-methylation of primary and secondary amines with different functional aldehydes. The obvious advantage of the presented method includes operational simplicity, high TON, the ready availability of the catalyst, and also good functional group compatibility. Since the simple catalyst system offers highly selective N-methylation under mild conditions but with Table 3 . Synthesis of Tertiary Amines by Ru/C-Catalyzed N-Methylation of Primary, Secondary Amines with Different Functional Aldehydes a a Reaction conditions: 10 mg of 5% Ru/C catalyst, 0.5 mmol of amine, 3 mmol of aldehyde, 5 mL of methanol. Yields and conversion were determined by GC using 1,3,5-trimethoxybenzenen as an internal standard based on amine. moderate reusability due to catalysts metal leaching, it would be useful and important for further investigation in the design and preparation of a highly stable Ru-based catalyst avoiding leaching. At present, our laboratory is conducting design and research on the prevention of catalyst leaching and other related aspects.

■ ASSOCIATED CONTENT * sı Supporting Information

Continuous chemoselective methylation of functionalized amines and diols with supercritical methanol over solid acid and acid-base bifunctional catalysts

Ruthenium-catalyzed direct methylation of primary and secondary aromatic amines using carbon dioxide and molecular hydrogen

Dimethylsulfoxide as an N-Methylation Reagent for Amines and Aromatic Nitro Compounds

Ruthenium-catalyzed reductive methylation of imines using carbon dioxide and molecular hydrogen

Top 200 Small Molecule Pharmaceuticals by Retail Sales

Expanding the Ligand Framework Diversity of Carbodicarbenes and Direct Detection of Boron Activation in the Methylation of Amines with CO 2

Expanding the Boundaries of Water-Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls

Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach

Selective formylation or methylation of amines using carbon dioxide catalysed by a rhodium perimidine-based NHC complex

Methylation of the C3' Amide of Taxanes: Synthesis of N

N-methylation versus oxidative addition using MeI in the reaction of organoplatinum(II) complexes containing pyrazine ligand

A General Method for N-Methylation of Amines and Nitro Compounds with Dimethylsulfoxide

The Chemistry of Dimethyl Carbonate

N-Methylation of amine and nitro compounds with CO 2 /H 2 catalyzed by Pd/CuZrO(x) under mild reaction conditions

Enhancing catalytic activity and stability for CO 2 methanation on Ni@MOF-5 via control of active species dispersion

Selective N-Methylation of N-Methylaniline with CO 2 and H 2 over TiO 2 -Supported PdZn Catalyst

Methylation of Amines with Methanol at Room Temperature

Efficient Cobalt-Catalyzed Methylation of Amines Using Methanol

N-Methylation of amines and nitroarenes with methanol using heterogeneous platinum catalysts

A pincer ligand enabled ruthenium catalyzed highly selective N-monomethylation of nitroarenes with methanol as the C1 source

Scalable direct Nmethylation of drug-like amines using 12 CO 2 / 13 CO 2 by simple inorganic base catalysis

Copper(II)-Catalyzed Selective Reductive Methylation of Amines with Formic Acid: An Option for Indirect Utilization of CO 2

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

Methylation of Amines and Ketones with Methanol Catalyzed by an Iridium Complex Bearing a 2-Hydroxypyridylmethylene Fragment

Effective N-methylation of nitroarenes with methanol catalyzed by a functionalized NHC-based iridium catalyst: a green approach to N-methyl amines

Improved and General Manganese-Catalyzed N-Methylation of

One-pot synthesis of N,Ndimethylaniline from nitrobenzene and methanol

One-pot synthesis of N,N-dimethylanilines from nitroarenes with skeletal Cu as chemoselective catalyst

Light-promoted N,Ndimethylation of amine and nitro compound with methanol catalyzed by Pd/TiO 2 at room temperature

Direct Methylation of Amines with Carbon Dioxide and Molecular Hydrogen using Supported Gold Catalysts

Photocatalytic N-Methylation of Amines over Pd/ TiO 2 for the Functionalization of Heterocycles and Pharmaceutical Intermediates

MOF-derived cobalt nanoparticles catalyze a general synthesis of amines

Facile synthesis of controllable graphene-co-shelled reusable Ni/NiO nanoparticles and their application in the synthesis of amines under mild conditions

RANEY® nickelcatalyzed reductive N-methylation of amines with paraformaldehyde: theoretical and experimental study

Commercial Pd/C-Catalyzed N-Methylation of Nitroarenes and Amines Using Methanol as Both C 1 and H 2 Source

Towards a general ruthenium-catalyzed hydrogenation of secondary and tertiary amides to amines