Production Of Primary Amines Research Articles

Practical electrochemical hydrogenation of nitriles at the nickel foam cathode.

We report a scalable hydrogenation method for nitriles based on cost-effective materials in a very simple two-electrode setup under galvanostatic conditions. All components are commercially and readily available. The method is very easy to conduct and applicable to a variety of nitrile substrates, leading exclusively to primary amine products in yields of up to 89% using an easy work-up protocol. Importantly, this method is readily transferable from the milligram scale in batch-type screening cells to the multi-gram scale in a flow-type electrolyser. The transfer to flow electrolysis enabled us to achieve a notable 20 g day-1 productivity of phenylethylamine at a geometric current density of 50 mA cm-2 in a flow-type electrolyser with 48 cm2 electrodes. It is noteworthy that this method is sustainable in terms of process safety and reusability of components.

Reductive Amination of Aldehyde and Ketone with Ammonia and H2 by an In Situ-Generated Cobalt Catalyst under Mild Conditions.

Herein, we present the simplest approach for the synthesis of primary amines via reductive amination using H2 as a reductant and aqueous ammonia as a nitrogen source, catalyzed by amorphous Co particles. The highly active Co particles were prepared in situ by simply mixing commercially available CoCl2 and NaBH4/NaHBEt3 without any ligand or support. This reaction system features mild conditions (80 °C, 1-10 bar), high selectivity (99%), a wide substrate scope, simple operation, and easy separation of the catalyst. The successful large-scale application of this reaction in the production of primary amines suggests its potential industrial interest.

Employing Ammonia for the Synthesis of Primary Amines: Recent Achievements over Heterogeneous Catalysts.

Primary amines represent highly privileged chemicals for synthesis of polymers, pharmaceuticals, agrochemicals, coatings, etc. Consequently, the development of efficient and green methodologies for the production of primary amines are of great importance in chemical industry. Owing to the advantages of low cost and ease in availability, ammonia is considered as a feasible nitrogen source for synthesis of N-containing compounds. Thus, the efficient transformation of ammonia into primary amines has received much attention. In this review, the commonly applied synthetic routes to produce primary amines from ammonia were summarized, including the reductive amination of carbonyl compounds, the hydrogen transfer amination of alcohols, the hydroamination of olefins and the arylation with ammonia, in which the catalytic performance of the recent heterogeneous catalysts is discussed. Additionally, various strategies to modulate the surface properties of catalysts are outlined in conjunction with the analysis of reaction mechanism. Particularly, the amination of the biomass-derived substrates is highlighted, which could provide competitive advantages in chemical industry and stimulate the development of sustainable catalysis in the future. Ultimately, perspectives into the challenges and opportunities for synthesis of primary amines with ammonia as N-resource are discussed.

Tailoring the d‐band centers enables NiM alloy to be multifunctional site for tandem reductive amination

AbstractIntegrating multi‐step reactions through tandem catalysis offers potential for efficient chemical engineering processes, but designing an efficient tandem catalyst is challenging. Herein, we report tailoring the d‐band centers of Ni through alloying with a second metal (M = Fe/Co/Cu/Ga), which enables it to be multifunctional site for tandem reductive amination. A linear correlation of d‐band center with yield of primary amine product was observed. Density functional theory and experiments revealed the upshifted d‐band center strengthened the adsorption of Schiff base intermediate in advantageous di(C&N) mode, also narrowed the adsorption energy gap between NH3 and H2. Furthermore, the multifunctional nanoparticles provide a confined space with short diffusion pathway for NH3* and H* to timely react with Schiff base. As a result, the NiFe/AlOx with a d‐band center nearest to the Fermi level exhibited the highest primary amine yield of 96.2% with five consecutive reusability under extremely low H2 pressure, which is superior to other reported precious‐metal‐based catalysts.

Programmable Amine Synthesis via Iterative Boron Homologation.

The value of Matteson-type reactions has been increasingly recognized for developing automated organic synthesis. However, the typical Matteson reactions almost exclusively focus on homologation of carbon units. Here, we report the detailed development of sequential insertion of nitrogen and carbon atoms into boronate C-B bonds, which provides a modular and iterative approach to access functionalized tertiary amines. A new class of nitrenoid reagents is uncovered to allow direct formation of aminoboranes from aryl or alkyl boronates via N-insertion. The one-pot N-insertion followed by controlled mono- or double-carbenoid insertion has been realized with widely available aryl boronates. The resulting aminoalkyl boronate products can undergo further homologation and various other transformations. Preliminary success on homologation of N,N-dialkylaminoboranes and sequential N- and C-insertions with alkyl boronates have also been achieved. To broaden the synthetic utility, selective removal of a benzyl or aryl substituent permits access to secondary or primary amine products. The application of this method has been demonstrated in the modular synthesis of bioactive compoundsand the programmable construction of diamines and aminoethers. A plausible reaction mechanism, supported by preliminary NMR (nuclear magnetic resonance) and computational studies, is also proposed.

Programmable Amine Synthesis via Iterative Boron Homologation

AbstractThe value of Matteson‐type reactions has been increasingly recognized for developing automated organic synthesis. However, the typical Matteson reactions almost exclusively focus on homologation of carbon units. Here, we report the detailed development of sequential insertion of nitrogen and carbon atoms into boronate C−B bonds, which provides a modular and iterative approach to access functionalized tertiary amines. A new class of nitrenoid reagents is uncovered to allow direct formation of aminoboranes from aryl or alkyl boronates viaN‐insertion. The one‐potN‐insertion followed by controlled mono‐ or double‐carbenoid insertion has been realized with widely available aryl boronates. The resulting aminoalkyl boronate products can undergo further homologation and various other transformations. Preliminary success on homologation ofN,N‐dialkylaminoboranes and sequentialN‐and C‐insertions with alkyl boronates have also been achieved. To broaden the synthetic utility, selective removal of a benzyl or aryl substituent permits access to secondary or primary amine products. The application of this method has been demonstrated in the modular synthesis of bioactive compounds and the programmable construction of diamines and aminoethers. A plausible reaction mechanism, supported by preliminary NMR (nuclear magnetic resonance) and computational studies, is also proposed.

Analysis of thermodynamics, kinetics, and reaction pathways in the amination of secondary alcohols over Ru/SiO2

This work considers the Ru-mediated amination of secondary alcohols with ammonia in vapor and liquid media. We map thermodynamic constraints, and we probe the impacts of species partial pressure, residence time, and reaction temperature on rate, selectivity, and catalyst stability. Alcohol amination consumes no H2, and H2 has no significant impact on amination kinetics; however, operating under H2 benefits Ru stability. Primary amine selectivity increases with ammonia pressure and alcohol conversion, and the latter observation is consistent with the formation of primary amines through a network of sequential reactions. Unfortunately, primary amines are susceptible to secondary deamination to form hydrocarbons. As is typical of processes that seek to isolate a reactive intermediate, the main selectivity challenge here is identifying residence times that are long enough to accumulate high substrate conversion but short enough to avoid secondary deamination. In general, moderate residence times will maximize the production of primary amines. Insights extend across a broad substrate scope, and we observe 70 – 90% yield of primary amines from linear, cyclic, and heterocyclic alcohols. That said, heterocyclic alcohols appear susceptible to product inhibition, so achieving high conversions requires longer residence times and/or increased ammonia pressures.

A Concerted Redox- and Light-Activated Agent for Controlled Multimodal Therapy against Hypoxic Cancer Cells.

Hypoxia represents a remarkably exploitable target for cancer therapy, is encountered only in solid human tumors, and is highly associated with cancer resistance and recurrence. Here, a hypoxia-activated mitochondria-accumulated Ru(II) polypyridyl prodrug functionalized with conjugated azo (Az) and nitrogen mustard (NM) functionalities, RuAzNM, is reported. This prodrug has multimodal theranostic properties toward hypoxic cancer cells. Reduction of the azo group in hypoxic cell microenvironments gives rise to the generation of two primary amine products, a free aniline mustard, and the polypyridyl RuNH2 complex. Thus, the aniline mustard triggers generation ofreactive oxygen species (ROS) and mtDNA crosslinking. Meanwhile, the resultant biologically benign phosphorescent RuNH2 gives rise to a diagnostic signal and signals activation of the phototherapy. This multimodal therapeutic effect eventually elevates ROS levels, depletes reduced nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP), and induces mitochondrial membrane damage, mtDNA damage, and ultimately cell apoptosis. This unique strategy allows controlled multimodal theranostics to be realized in hypoxic cells and multicellular spheroids, making RuAzNM a highly selective and effective cancer-cell-selective theranostic agent (IC50 = 2.3µm for hypoxic HepG2 cancer cells vs 58.2µm for normoxic THL-3 normal cells). This is the first report of a metal-based compound developed as a multimodal theranostic agent for hypoxia.

Selective electrochemical reductive amination of benzaldehyde at heterogeneous metal surfaces

Ammonia is one of the largest-volume commodity chemicals, and electrochemical routes to ammonia utilization are appealing due to increasingly available renewable electricity. In this work, we demonstrate an electrochemical analog to reductive amination for the synthesis of benzylamine from benzaldehyde and ammonia. Previous works on electrochemical reductive amination have generally focused on proof-of-concept outer-sphere routes. In our system, imine hydrogenation proceeds via an inner-sphere route on an Ag electrocatalyst at ambient conditions with an initial Faradaic efficiency toward the primary amine product of ∼80% and partial current greater than 4 mA/cm2 at −1.96 V versus Fc/Fc+ (−1.36 V versus the normal hydrogen electrode). Ag was selected after evaluating diverse transition metal electrocatalysts, and the rate-determining step was the initial electron transfer to the imine. Overall, this work represents a step toward inner-sphere electrochemical reductive amination systems, opening a large phase space of heterogeneous electrocatalysts for reactions that currently rely on thermochemical routes.

Highly selective synthesis of primary amines from amide over Ru-Nb2 O5 catalysts.

Amines are an important class of compounds in natural products and medicines. The universal availability of amides provides a potential way for the synthesis of amines. Herein, Ru/Nb2 O5 catalyst is demonstrated to be highly efficient and stable for the selective hydrogenation of propionamide to propylamine (as a model reaction), with up to 91.4% yield of propylamine under relatively mild conditions. Results from XPS analyses, CO chemisorption, TEM images and DRIFTS spectra revealed that the unique properties of Nb2 O5 can effectively activate the C=O group of amides, and the smaller Ru particles on Nb2 O5 could further promote the activation, leading to superior catalytic performance of Ru/Nb2 O5 for amide hydrogenation. Meanwhile, reducing the surface acidity of Nb2 O5 can greatly inhibit the side reactions to by-products, and further enhance the selectivity to amine. Moreover, this catalytic system is also applicable for the hydrogenation of a variety of amides and provides high potential for the industrial production of primary amines from amides.

Spectrophotometric Determination of Mebendazole using Diazotization Reaction and Coupling with m-Aminophenol Reagent

A simple and sensitive spectrophotometric method has been developed for the determination of mebendazole (MBZ) in it's pure and tablet form. The method is based on alkaline hydrolysis of MBZ with sodium hydroxide to give primary amine product which reacts with sodium nitrite in an acidic medium (hydrochloric acid) to yield diazotized mebendazole (D-MBZ) which is coupling with m-aminophenol reagent (mAP) to form an azo dye. The absorbance of the azo dye for this suggested method (yellow dye) has been measured at 360 nm. Beer's law for this proposed method is in the range of (0.5-20 µg.ml-1), the molar absorptivity value is 1.63×104 L.mol-1.cm-1 and the Sandell's value index is calculated and equal to 0.018 μg.cm- 2. Also, the limit of detection and the limit of quantification are calculated and equal to 0.1718 μg.ml-1 and 0.5726µg.ml-1 respectively. The ratio of the formed azo dye [D-MBZ: mAP] is [2: 1].

Facile and Efficient Synthesis of Primary Amines via Reductive Amination over a Ni/Al2O3 Catalyst

The production of primary amines with high efficiency and selectivity employing appropriate catalysts is of central importance yet challenging. Here, we reported Ni nanoparticles supported on γ-Al2O3 as a highly active heterogeneous catalyst for the synthesis of primary amines through reductive amination in the presence of ammonia and hydrogen. The resulting Ni/Al2O3 catalyst exhibited outstanding performance for the selective reductive amination of carbonyl compounds (aldehydes and ketones) involving aromatic, branched, and purely aliphatic chemicals converted into their corresponding primary amines with excellent yields (87∼99%) under mild reaction conditions (100 °C and 2 MPa), which was attributed to the synergistic effect of strong metal–support interaction combined with medium acidic sites. In particular, the yield of primary amines for earth-abundant Ni catalysts was superior to that for precious metal catalysts (Ru, Rh, and Pd), suggesting that the Ni/Al2O3 catalyst could be a promising candidate for the industrial production of amines.

Electrochemical Aziridination of Tetrasubstituted Alkenes with Ammonia

Ammonia (NH3) is an ideal nitrogen source in terms of availability, reactivity, safety, atom economy, environmental compatibility, and ease of isolation. However, its utility for amine synthesis is...

Selective Hydrogenation of Fatty Nitriles to Primary Fatty Amines: Catalyst Evaluation and Optimization Starting from Octanenitrile

AbstractIn this contribution, an evaluation of the potential of various homogeneous and heterogeneous catalysts for a selective hydrogenation of fatty nitriles toward primary amines is reported exemplified for the conversion of octanenitrile into octane‐1‐amine as a model reaction. When using heterogeneous catalysts such as the ruthenium catalyst Ru/C, the palladium catalyst Pd/C, and the platinum catalyst Pt/Al2O3, low selectivities in the hydrogenation are observed, thus leading to a large portion of secondary and tertiary amine side‐products. For example, when using Ru/C as a heterogeneous catalyst, high conversions of up to 99% are obtained but the selectivity remains low with a percentage of the primary amine being at 60% at the highest. The study further reveals a high potential of homogeneous ruthenium and manganese catalysts. When also taking into account economical considerations with respect to the metal price, in particular, manganese catalysts turn out to be attractive for the desired transformation and their application in the model reaction leads to the desired primary amine product with excellent conversion, selectivity, and high yield.Practical Applications: This work describes an optimized hydrogenation process for transforming fatty nitriles to their corresponding primary amines. In general, fatty amines belong to the most applied fatty acid‐derived compounds in the chemical industry with an annual product volume exceeding 800 000 tons per year in 2011 and are widely required in the chemical industry since such compounds are either directly used in home products such as fabric softeners, dishwashing liquids, car wash detergents, or carpet cleaners or in a broad range of industrial products, for example, lubricating additives, flotation agents, dispersants, emulsifiers, corrosion inhibitors, fungicides, and bactericides, showing additional major applications, e.g., in the detergents industry. Among them primary amines play an important industrial role. However, a major concern of current processes is the lack of selectivity and the formation of secondary and tertiary amines as side‐products. By modifying a recently developed catalytic system based on manganese as economically attractive and environmentally benign metal component an efficient and selective access to fatty amines when starting from the corresponding nitriles is achieved. For example, hydrogenation of octanenitrile leads to a synthesis of octane‐1‐amine with >99% conversion and excellent selectivity with formation of secondary and tertiary amine side‐products being suppressed to an amount of <1%.

Zirconium Hydroaminoalkylation. An Alternative Disconnection for the Catalytic Synthesis of α-Arylated Primary Amines.

Primary amine products have been prepared using zirconium-catalyzed hydroaminoalkylation of alkenes with N-silylated benzylamine substrates. Catalysis using commercially available Zr(NMe2)4 affords an alternative disconnection to access α-arylated primary amines upon aqueous workup. Substrate-dependent regio- and diastereoselectivity of the reaction is observed. Bulky substituents on the terminal alkene exclusively generate the linear regioisomer. This atom-economic catalytic strategy for the synthesis of building blocks that can undergo further synthetic elaboration is highlighted in the preparation of trifluoroethylated α-arylated amines.

Catalyst: Is the Amino Acid a New Frontier for Biorefineries?

Prof. Ning Yan obtained his BS and PhD degrees from Peking University in 2004 and 2009, respectively. Thereafter, he worked as a Marie-Curie research fellow at Ecole Polytechnique Federale de Lausanne, Switzerland. He joined the National University of Singapore (NUS) as an assistant professor, established the Lab of Green Catalysis in 2012, and was promoted to the position of associate professor in 2018. Yunzhu Wang received her BE degree from NUS in 2014. She joined Prof. Yan’s group in the same year and is currently pursuing her PhD. Her research interests include nanoscale metal catalysts and their applications in producing renewable nitrogen-containing chemicals.

Supported Ni Catalyst for Liquid Phase Hydrogenation of Adiponitrile to 6-Aminocapronitrile and Hexamethyenediamine.

Supported Ni catalysts prepared under different conditions, for liquid phase hydrogenation of adiponitrile (ADN) to 6-aminocapronitrile (ACN) and hexamethyenediamine (HMD), were investigated. The highly reactive imine intermediate can form condensation byproducts with primary amine products (ACN and HMD), which decreased the yield coefficient of primary amines. The catalysts support, condition of catalyst preparation and dosage of additive were studied to improve the yield. A highly dispersed Ni/SiO2 catalyst prepared by the direct reduction of Ni(NO3)2/SiO2 suppressed the condensation reactions by promoting the hydrogenation of adsorbed imines, and it gave the improved hydrogenation activity of 0.63 mol·kgcat−1·min−1 and primary amine selectivity of 94% when NaOH was added into the reactor.

A high performance catalyst of shape-specific ruthenium nanoparticles for production of primary amines by reductive amination of carbonyl compounds.

The creation of metal catalysts with highly active surfaces is pivotal to meeting the strong economic demand of the chemical industry. Specific flat-shaped pristine fcc ruthenium nanoparticles having a large fraction of atomically active {111} facets exposed on their flat surfaces have been developed that act as a highly selective and reusable heterogeneous catalyst for the production of various primary amines at exceedingly high reaction rates by the low temperature reductive amination of carbonyl compounds. The high performance of the catalyst is attributed to the large fraction of metallic Ru serving as active sites with weak electron donating ability that prevail on the surface exposed {111} facets of flat-shaped fcc Ru nanoparticles. This catalyst exhibits a highest turnover frequency (TOF) of ca. 1850 h-1 for a model reductive amination of biomass derived furfural to furfurylamine and provides a reaction rate approximately six times higher than that of an efficient and selective support catalyst of Ru-deposited Nb2O5 (TOF: ca. 310 h-1).

Influence of acid-base properties of the support on the catalytic performances of Pt-based catalysts in a gas-phase hydrogenation of acetonitrile

Catalytic performances of Pt-based catalysts supported on various oxides (Al2O3, MgO, SiO2, and CeO2) prepared by a sol-gel method were evaluated by gas-phase hydrogenation of acetonitrile, in order to investigate the influence of acid-base properties of support oxides on products distribution. Acid-base properties were studied by pyridine adsorption followed by FTIR (Lewis and Brønsted acidity), 3,3-dimethyl-1-butene isomerization (Brønsted acidity), and temperature-programmed desorption (TPD) of CO2 (basicity). The results obtained concerning acid-base characterization of the oxides in this paper show a reasonable scale of surface acidity and basicity, as MgO and CeO2 are known to be basic oxides, silica is expected to be a neutral support according the preparation procedure, whereas alumina is an amphoteric one.The performances of the four tested catalysts in terms of the selectivity towards the primary amine are correlated with the amount of basic sites. The more basic the support is, the more it favors the production of primary amines.

Production of Primary Amines by Reductive Amination of Biomass-Derived Aldehydes/Ketones.

Transformation of biomass into valuable nitrogen-containing compounds is highly desired, yet limited success has been achieved. Here we report an efficient catalyst system, partially reduced Ru/ZrO2 , which could catalyze the reductive amination of a variety of biomass-derived aldehydes/ketones in aqueous ammonia. With this approach, a spectrum of renewable primary amines was produced in good to excellent yields. Moreover, we have demonstrated a two-step approach for production of ethanolamine, a large-market nitrogen-containing chemical, from lignocellulose in an overall yield of 10 %. Extensive characterizations showed that Ru/ZrO2 -containing multivalence Ru association species worked as a bifunctional catalyst, with RuO2 as acidic promoter to facilitate the activation of carbonyl groups and Ru as active sites for the subsequent imine hydrogenation.