Cobalt nanoparticle-catalysed N-alkylation of amides with alcohols.

A protocol for efficient N-alkylation of benzamides with alcohols in the presence of cobalt-nanocatalysts is described. Key to the success of this general methodology is the use of highly dispersed cobalt nanoparticles supported on carbon, which are obtained from the pyrolysis of cobalt(ii) acetate and o-phenylenediamine as a ligand at suitable temperatures. The catalytic material shows a broad substrate scope and good tolerance to functional groups. Apart from the synthesis of a variety of secondary amides (>45 products), the catalyst allows for the conversion of more challenging aliphatic alcohols and amides, including biobased and macromolecular amides. The practical applicability of the catalyst is underlined by the successful recycling and reusability.

A general and robust Ni-based nanocatalyst for selective hydrogenation reactions at low temperature and pressure.

Catalytic hydrogenations are important and widely applied processes for the reduction of organic compounds both in academic laboratories and in industry. To perform these reactions in sustainable and practical manner, the development and applicability of non-noble metal-based heterogeneous catalysts is crucial. Here, we report highly active and air-stable nickel nanoparticles supported on mesoporous silica (MCM-41) as a general and selective hydrogenation catalyst. This catalytic system allows for the hydrogenation of carbonyl compounds, nitroarenes, N-heterocycles, and unsaturated carbon─carbon bonds in good to excellent selectivity under very mild conditions (room temperature to 80°C, 2 to 10 bar H2). Furthermore, the optimal nickel/meso-silicon dioxide catalyst is reusable (4 cycles) without loss of its catalytic activity.

Streamlining the synthesis of amides using Nickel-based nanocatalysts.

The synthesis of amides is a key technology for the preparation of fine and bulk chemicals in industry, as well as the manufacture of a plethora of daily life products. Furthermore, it constitutes a central bond-forming methodology for organic synthesis and provides the basis for the preparation of numerous biomolecules. Here, we present a robust methodology for amide synthesis compared to traditional amidation reactions: the reductive amidation of esters with nitro compounds under additives-free conditions. In the presence of a specific heterogeneous nickel-based catalyst a wide range of amides bearing different functional groups can be selectively prepared in a more step-economy way compared to previous syntheses. The potential value of this protocol is highlighted by the synthesis of drugs, as well as late-stage modifications of bioactive compounds. Based on control experiments, material characterizations, and DFT computations, we suggest metallic nickel and low-valent Ti-species to be crucial factors that makes this direct amide synthesis possible.

Catalytic utilization of converter gas - an industrial waste for the synthesis of pharmaceuticals.

Converter gas is a large scale waste product that is usually burned to carbon dioxide and contributes to the world emission of greenhouse gases. Herein we demonstrate that instead of burning the converter gas can be used as a reducing agent in organic reactions to produce valuable pharmaceuticals and agrochemicals. In particular, amide-based selected drug molecules have been synthesized by a reaction of aromatic nitro compounds and carboxylic acids in the presence of converter gas. In addition, we showed that this gas can also be conveniently utilized to carryout classical reductive amination reaction.

Methanol as a Potential Hydrogen Source for Reduction Reactions Enabled by a Commercial Pt/C Catalyst.

Catalytic reduction reactions using methanol as a transfer hydrogenating agent is gaining significant attention because this simple alcohol is inexpensive and produced on a bulk scale. Herein, we report the catalytic utilization of methanol as a hydrogen source for the reduction of different functional organic compounds such as nitroarenes, olefins, and carbonyl compounds. The key to the success of this transformation is the use of a commercially available Pt/C catalyst, which enabled the transfer hydrogenation of a series of simple and functionalized nitroarenes-to-anilines, alkenes-to-alkanes, and aldehydes-to-alcohols using methanol as both the solvent and hydrogen donor. The practicability of this Pt-based protocol is showcased by demonstrating catalyst recycling and reusability as well as reaction upscaling. In addition, the Pt/C catalytic system was also adaptable for the N-methylation and N-alkylation of anilines via the borrowing hydrogen process. This work provides a simple and flexible approach to prepare a variety of value-added products from readily available methanol, Pt/C, and other starting materials.

Development of a General and Selective Nanostructured Cobalt Catalyst for the Hydrogenation of Benzofurans, Indoles and Benzothiophenes.

The selective hydrogenation of benzofurans in the presence of a heterogeneous non-noble metal catalyst is reported. The developed optimal catalytic material consists of cobalt-cobalt oxide core-shell nanoparticles supported on silica, which has been prepared by the immobilization and pyrolysis of cobalt-DABCO-citric acid complex on silica under argon at 800 °C. This novel catalyst allows for the selective hydrogenation of simple and functionalized benzofurans to 2,3-dihydrobenzofurans as well as related heterocycles. The versatility of the reported protocol is showcased by the reduction of selected drugs and deuteration of heterocycles. Further, the stability, recycling, and reusability of the Co-nanocatalyst are demonstrated.

Stable and reusable Ni-based nanoparticles for general and selective hydrogenation of nitriles to amines.

Silica supported ultrasmall Ni-nanoparticles allow for general and selective hydrogenation of all kinds of nitriles to primary amines under mild conditions. By calcination of a template material generated from Ni(ii)nitrate and colloidal silica under air and subsequent reduction in the presence of molecular hydrogen the optimal catalyst is prepared. The prepared supported nanoparticles are stable, can be conveniently used and easily recycled. The applicability of the optimal catalyst material is shown by hydrogenation of >110 diverse aliphatic and aromatic nitriles including functionalized and industrially relevant substrates. Challenging heterocyclic nitriles, specifically cyanopyridines, provided the corresponding primary amines in good to excellent yields. The resulting amines serve as important precursors and intermediates for the preparation of numerous life science products and polymers.

Nickel-catalyzed hydrogenative coupling of nitriles and amines for general amine synthesis.

Efficient and general methods for the synthesis of amines remain in high demand in the chemical industry. Among the many known processes, catalytic hydrogenation is a cost-effective and industrially proven reaction and currently used to produce a wide array of such compounds. We report a homogeneous nickel catalyst for hydrogenative cross coupling of a range of aromatic, heteroaromatic, and aliphatic nitriles with primary and secondary amines or ammonia. This general hydrogenation protocol is showcased by straightforward and highly selective synthesis of >230 functionalized and structurally diverse amines including pharmaceutically relevant and chiral products, as well as 15N-isotope labeling applications.

Single-Atom (Iron-Based) Catalysts: Synthesis and Applications.

Supported single-metal atom catalysts (SACs) are constituted of isolated active metal centers, which are heterogenized on inert supports such as graphene, porous carbon, and metal oxides. Their thermal stability, electronic properties, and catalytic activities can be controlled via interactions between the single-metal atom center and neighboring heteroatoms such as nitrogen, oxygen, and sulfur. Due to the atomic dispersion of the active catalytic centers, the amount of metal required for catalysis can be decreased, thus offering new possibilities to control the selectivity of a given transformation as well as to improve catalyst turnover frequencies and turnover numbers. This review aims to comprehensively summarize the synthesis of Fe-SACs with a focus on anchoring single atoms (SA) on carbon/graphene supports. The characterization of these advanced materials using various spectroscopic techniques and their applications in diverse research areas are described. When applicable, mechanistic investigations conducted to understand the specific behavior of Fe-SACs-based catalysts are highlighted, including the use of theoretical models.

Ambient Hydrogenation and Deuteration of Alkenes Using a Nanostructured Ni-Core-Shell Catalyst.

A general protocol for the selective hydrogenation and deuteration of a variety of alkenes is presented. Key to success for these reactions is the use of a specific nickel-graphitic shell-based core-shell-structured catalyst, which is conveniently prepared by impregnation and subsequent calcination of nickel nitrate on carbon at 450 °C under argon. Applying this nanostructured catalyst, both terminal and internal alkenes, which are of industrial and commercial importance, were selectively hydrogenated and deuterated at ambient conditions (room temperature, using 1 bar hydrogen or 1 bar deuterium), giving access to the corresponding alkanes and deuterium-labeled alkanes in good to excellent yields. The synthetic utility and practicability of this Ni-based hydrogenation protocol is demonstrated by gram-scale reactions as well as efficient catalyst recycling experiments.

Reusable Co-nanoparticles for general and selective N-alkylation of amines and ammonia with alcohols.

A general cobalt-catalyzed N-alkylation of amines with alcohols by borrowing hydrogen methodology to prepare different kinds of amines is reported. The optimal catalyst for this transformation is prepared by pyrolysis of a specific templated material, which is generated in situ by mixing cobalt salts, nitrogen ligands and colloidal silica, and subsequent removal of silica. Applying this novel Co-nanoparticle-based material, >100 primary, secondary, and tertiary amines including N-methylamines and selected drug molecules were conveniently prepared starting from inexpensive and easily accessible alcohols and amines or ammonia.

Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines.

Reductive aminations constitute an important class of reactions widely applied in research laboratories and industries for the synthesis of amines as well as pharmaceuticals, agrochemicals and biomolecules. In particular, catalytic reductive aminations using molecular hydrogen are highly valued and essential for the cost-effective and sustainable production of different kinds of amines and their functionalization. These reactions couple easily accessible carbonyl compounds (aldehydes or ketones) with ammonia, amines or nitro compounds in the presence of suitable catalysts and hydrogen that enable the preparation of linear and branched primary, secondary and tertiary amines including N-methylamines and molecules used in life science applications. In general, amines represent valuable fine and bulk chemicals, which serve as key precursors and central intermediates for the synthesis of advanced chemicals, life science molecules, dyes and polymers. Noteworthily, amine functionalities are present in a large number of pharmaceuticals, agrochemicals and biomolecules, and play vital roles in the function of these active compounds. In general, reductive aminations are challenging processes, especially for the syntheses of primary amines, which often are non-selective and suffer from over-alkylation and reduction of carbonyl compounds to the corresponding alcohols. Hence, the development of suitable catalysts to perform these reactions in a highly efficient and selective manner is crucial and continues to be important and attracts scientific interest. In this regard, both homogeneous and heterogeneous catalysts have successfully been developed for these reactions to access various amines. There is a need for a comprehensive review on catalytic reductive aminations to discuss the potential catalysts used and applicability of this methodology in the preparation of different kinds of amines, which are of commercial, industrial and medicinal importance. Consequently, in this review we discuss catalytic reductive aminations using molecular hydrogen and their applications in the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic primary, secondary and tertiary amines as well as N-methylamines and more complex drug targets. In addition, mechanisms of reductive aminations including selective formation of desired amine products as well as possible side reactions are emphasized. This review aims at the scientific communities working in the fields of organic synthesis, catalysis, and medicinal and biological chemistry.

A General Catalyst Based on Cobalt Core-Shell Nanoparticles for the Hydrogenation of N-Heteroarenes Including Pyridines.

Herein, we report the synthesis of specific silica-supported Co/Co3 O4 core-shell based nanoparticles prepared by template synthesis of cobalt-pyromellitic acid on silica and subsequent pyrolysis. The optimal catalyst material allows for general and selective hydrogenation of pyridines, quinolines, and other heteroarenes including acridine, phenanthroline, naphthyridine, quinoxaline, imidazo[1,2-a]pyridine, and indole under comparably mild reaction conditions. In addition, recycling of these Co nanoparticles and their ability for dehydrogenation catalysis are showcased.

Reductive amination using cobalt-based nanoparticles for synthesis of amines.

Reductive aminations are an essential class of reactions widely applied for the preparation of different kinds of amines, as well as a number of pharmaceuticals and industrially relevant compounds. In such reactions, carbonyl compounds (aldehydes, ketones) react with ammonia or amines in the presence of a reducing agent and form corresponding amines. Common catalysts used for reductive aminations, especially for the synthesis of primary amines, are based on precious metals or Raney nickel. However, their drawbacks and limited applicability inspired us to look for alternative catalysts. The development of base-metal nanostructured catalysts is highly preferable and is crucial to the advancement of sustainable and cost-effective reductive amination processes. In this protocol, we describe the preparation of carbon-supported cobalt-based nanoparticles as efficient and practical catalysts for synthesis of different kinds of amines by reductive aminations. Template synthesis of a cobalt-triethylenediamine-terephthalic acid metal-organic framework on carbon and subsequent pyrolysis to remove the organic template resulted in the formation of supported single cobalt atoms and nanoparticles. Applying these catalysts, we have synthesized structurally diverse benzylic, aliphatic and heterocyclic primary, secondary and tertiary amines, including pharmaceutically relevant products, starting from inexpensive and easily accessible carbonyl compounds with ammonia, nitro compounds or amines and molecular hydrogen. To prepare this cobalt-based catalyst takes 26 h, and the reported catalytic reductive amination reactions can be carried out within 18-28 h.

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.

General and selective synthesis of primary amines using Ni-based homogeneous catalysts.

The development of base metal catalysts for industrially relevant amination and hydrogenation reactions by applying abundant and atom economical reagents continues to be important for the cost-effective and sustainable synthesis of amines which represent highly essential chemicals. In particular, the synthesis of primary amines is of central importance because these compounds serve as key precursors and central intermediates to produce value-added fine and bulk chemicals as well as pharmaceuticals, agrochemicals and materials. Here we report a Ni-triphos complex as the first Ni-based homogeneous catalyst for both reductive amination of carbonyl compounds with ammonia and hydrogenation of nitroarenes to prepare all kinds of primary amines. Remarkably, this Ni-complex enabled the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic linear and branched primary amines as well as aromatic primary amines starting from inexpensive and easily accessible carbonyl compounds (aldehydes and ketones) and nitroarenes using ammonia and molecular hydrogen. This Ni-catalyzed reductive amination methodology has been applied for the amination of more complex pharmaceuticals and steroid derivatives. Detailed DFT computations have been performed for the Ni-triphos based reductive amination reaction, and they revealed that the overall reaction has an inner-sphere mechanism with H2 metathesis as the rate-determining step.

Homogeneous cobalt-catalyzed reductive amination for synthesis of functionalized primary amines.

The development of earth abundant 3d metal-based catalysts continues to be an important goal of chemical research. In particular, the design of base metal complexes for reductive amination to produce primary amines remains as challenging. Here, we report the combination of cobalt and linear-triphos (bis(2-diphenylphosphinoethyl)phenylphosphine) as the molecularly-defined non-noble metal catalyst for the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds, gaseous ammonia and hydrogen in good to excellent yields. Noteworthy, this cobalt catalyst exhibits high selectivity and as a result the -NH2 moiety is introduced in functionalized and structurally diverse molecules. An inner-sphere mechanism on the basis of the mono-cationic [triphos-CoH]+ complex as active catalyst is proposed and supported with density functional theory computation on the doublet state potential free energy surface and H2 metathesis is found as the rate-determining step.

Nickel-Catalyzed Stereodivergent Synthesis of E- and Z-Alkenes by Hydrogenation of Alkynes.

A convenient protocol for stereodivergent hydrogenation of alkynes to E- and Z-alkenes by using nickel catalysts was developed. Simple Ni(NO3 )2 ⋅6 H2 O as a catalyst precursor formed active nanoparticles, which were effective for the semihydrogenation of several alkynes with high selectivity for the Z-alkene (Z/E>99:1). Upon addition of specific multidentate ligands (triphos, tetraphos), the resulting molecular catalysts were highly selective for the E-alkene products (E/Z>99:1). Mechanistic studies revealed that the Z-alkene-selective catalyst was heterogeneous whereas the E-alkene-selective catalyst was homogeneous. In the latter case, the alkyne was first hydrogenated to a Z-alkene, which was subsequently isomerized to the E-alkene. This proposal was supported by density functional theory calculations. This synthetic methodology was shown to be generally applicable in >40 examples and scalable to multigram-scale experiments.

Reusable Nickel Nanoparticles-Catalyzed Reductive Amination for Selective Synthesis of Primary Amines.

The preparation of nickel nanoparticles as efficient reductive amination catalysts by pyrolysis of in situ generated Ni-tartaric acid complex on silica is presented. The resulting stable and reusable Ni-nanocatalyst enables the synthesis of functionalized and structurally diverse primary benzylic, heterocyclic and aliphatic amines starting from inexpensive and readily available carbonyl compounds and ammonia in presence of molecular hydrogen. Applying this Ni-based amination protocol, -NH2 moiety can be introduced in structurally complex compounds, for example, steroid derivatives and pharmaceuticals.

Cobalt-based nanoparticles prepared from MOF-carbon templates as efficient hydrogenation catalysts.

The development of efficient and selective nanostructured catalysts for industrially relevant hydrogenation reactions continues to be an actual goal of chemical research. In particular, the hydrogenation of nitriles and nitroarenes is of importance for the production of primary amines, which constitute essential feedstocks and key intermediates for advanced chemicals, life science molecules and materials. Herein, we report the preparation of graphene shell encapsulated Co3O4- and Co-nanoparticles supported on carbon by the template synthesis of cobalt-terephthalic acid MOF on carbon and subsequent pyrolysis. The resulting nanoparticles create stable and reusable catalysts for selective hydrogenation of functionalized and structurally diverse aromatic, heterocyclic and aliphatic nitriles, and as well as nitro compounds to primary amines (>65 examples). The synthetic and practical utility of this novel non-noble metal-based hydrogenation protocol is demonstrated by upscaling several reactions to multigram-scale and recycling of the catalyst.