High performance of nitrogen-doped carbon-supported cobalt catalyst for the mild and selective synthesis of primary amines

A nitrogen-doped carbon-supported Co catalyst (Co/N-C-800) was discovered to be highly active for the reductive amination of carbonyl compounds with NH₃ and the hydrogenation of nitriles into primary amines using H₂ as the hydrogen source. Structurally diverse carbonyl compounds were selectively transformed into primary amines with good to excellent yields (82.8–99.6%) under mild conditions. The Co/N-C-800 catalyst showed comparable or better catalytic performance than the reported noble metal catalysts. The Co/N-C-800 catalyst also showed high activity for the hydrogenation of nitriles, affording the corresponding primary amines with high yields (81.7–99.0%). An overall reaction mechanism is proposed for the reductive amination of benzaldehyde and the hydrogenation of benzonitrile, which involves the same intermediates of phenylmethanimine and N-benzylidenebenzylamine.     

Fast Reductive Amination by Transfer Hydrogenation “on Water”

Reductive amination of various ketones and aldehydes by transfer hydrogenation under aqueous conditions has been developed, by using cyclometallated iridium complexes as catalysts and formate as hydrogen source. The pH value of the solution is shown to be critical for a high catalytic chemoselectivity and activity, with the best pH value being 4.8. In comparison with that in organic solvents, the reductive amination in an aqueous phase is faster, and the molar ratio of the substrate to the catalyst (S/C) can be set as high as 1×10⁵, the highest S/C value ever reported in reductive amination reactions. The catalyst is easy to access and the reaction is operationally simple, allowing a wide range of ketones and aldehydes to react with various amines in high yields. The protocol provides a practical and environmental friendly new method for the synthesis of amine compounds.     

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1)

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).     

Strategy for the synthesis of polymeric supports with hydrazone linkers for solid-phase alkylation of ketones and aldehydes

A new approach to polymeric supports useful for the immobilization of aldehydes and ketones via hydrazone linkers is reported. The new strategy gives supports with better properties and is effective for the synthesis of all supports previously used for the alkylation of ketones anchored as hydrazones. In contrast to other approaches, the new strategy also provided a polymer with an economical C2 spacer linker. The supports were used for immobilization of ketones 3-pentanone, acetone, N-benzylpiperidone, and aldehydes hexanal and 3-phenylpropanal in the form of their hydrazones. The polymer-supported hydrazones were subjected to alpha-alkylation (LDA/RX) followed by acidic, reductive, or oxidative cleavage/workup procedures to provide alpha-alkylated aldehydes or ketones as well as corresponding primary amines, alcohols, nitriles or acids.     

Synthesis of novel serotonergics and other N-alkylamines using simple reductive amination using catalytic hydrogenation with Pd/C

Formation of N-alkylated α-methyltryptamine derivatives (2) was accomplished by simple reductive amination of amine (1) with ketones using catalytic hydrogenation conditions (3 atm H₂ and 10% Pd on carbon). This method was also applied to other primary and secondary amines using ketones and aldehydes.     

Direct Reductive Amination of Aldehydes and Ketones with 2,4-Ionene-Based Borohydride Exchange Resin as a Novel Polymer-Supported Reducing Agent

Direct reductive amination of aldehydes and ketones were accomplished efficiently using high-capacity, ionene-based, polymer-supported borohydride reagent in isopropyl alcohol at reflux under neutral conditions. The reagent is easily prepared by mixing aqueous solution of 2,4-ionene bromide with an alkaline solution of sodium borohydride at room temperature. The generality of reaction was established using both aliphatic and aromatic aldehydes, ketones, and amines.     

Polymer-supported triacetoxyborohydride: a novel reagent of choice for reductive amination

A novel polymer-supported triacetoxyborohydride reagent for reductive amination of aldehydes and ketones is reported. The bound reagent was found to be shelf-stable and provided broad scope and reactivity in reductive amination reactions under mild reaction conditions. Streamlined protocols for its application in reductive amination reactions using both primary and secondary amines are described.     

An efficient and versatile synthesis of aromatic nitriles from aldehydes

A simple and direct method has been developed for synthesis of nitriles based on one-pot reaction of aromatic aldehydes with three different kind of reagents:CeCl₃7H₂O/KI/H₂O₂,CeCl₃·7H₂O/KI/UHP and（NH₄）₂Ce（NO₃）₆/KI/H₂O₂ in aqueous ammonia.     

General Reductive Amination of Aldehydes and Ketones with Amines and Nitroaromatics under H2 by Recyclable Iridium Catalysts

Heterogeneous iridium catalysts were prepared and applied for the reductive amination of aldehydes and ketones with nitroaromatics and amines using H₂ . The iridium catalysts were prepared by pyrolysis of ionic liquid 1‐methyl‐3‐cyanomethylimidazoulium chloride ([MCNI ]Cl) with iridium chloride (IrCl₃ ) in activated carbons. Iridium particles were well dispersed and stable in the N‐doped carbon materials from [MCNI ]Cl with activated carbon. The Ir@NC (600‐2h) catalyst was found to be highly active and selective for the reductive amination of aldehydes and ketones using H₂ and a variety of nitrobenzenes and amines were selectively converted into the corresponding secondary and tertiary amines. The Ir@NC (600‐2h) catalyst can be reusable several times without evident deactivation.     

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.

A Ni-triphos based homogeneous catalyst enabled the synthesis of all kinds of primary amines by reductive amination of carbonyl compounds with ammonia and hydrogenation of nitroarenes.     

ZrCl4/Hantzsch 1,4-dihydropyridine as a new and efficient reagent combination for the direct reductive amination of aldehydes and ketones with weakly basic amines

ZrCl4/Hantzsch 1,4-dihydropyridine is a mild and highly efficient reagent combination for the direct reductive amination.Weakly basic amines such as anilines substituted by electron-withdrawing group and heteroaromatic amines can be reductivelyalkylated with electron rich aldehydes and ketones under mild conditions to form the secondary amines in excellent yields.     

Synthesis of [11C]/(13C)amines via carbonylation followed by reductive amination

Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by reductive amination. The 11C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or aryl triflates, [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in this step were then transformed directly into amines by reductive amination using different amines in the presence of TiCl4 and NaBH3CN. The 11C-labelled amines were obtained with decay-corrected radiochemical yields in the range 2-78%. The radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl-phenyl-amine was synthesised and analysed by NMR spectroscopy for confirmation of the labelling position. Specific radioactivity was determined for the same compound. The reference compounds were prepared by reductive amination of ketones using conventional reaction conditions and three of the compounds were novel. The presented approach is a new method for the synthesis of [11C]/(13C)amines.     

Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.     

A direct synthesis of nitriles and amides from aldehydes using dry or wet alumina in solvent free conditions

An efficient and simple procedure for the direct conversion of aldehydes into the corresponding nitriles with NH₂OH·HCl/dry Al₂O₃/MeSO₂Cl or amides with NH₂OH·HCl/wet Al₂O₃/MeSO₂Cl are studied.     

Synthesis of primary amines: first homogeneously catalyzed reductive amination with ammonia

[reaction: see text] The synthesis of primary amines via reductive amination of the corresponding carbonyl compounds with aqueous ammonia is achieved for the first time with soluble transition metal complexes. Up to an 86% yield and a 97% selectivity for benzylamines were obtained in the case of various benzaldehydes by using a Rh-catalyst together with water-soluble phosphine and ammonium acetate. In the case of aliphatic aldehydes, a bimetallic catalyst based on Rh/Ir gave improved results.     

Reductive amination using ammonia borane

A variety of primary, secondary, and tertiary amines were prepared in 84-95% yields using ammonia borane for the reductive amination of aldehydes and ketones in the presence of titanium isopropoxide.     

A one-pot process for the enantioselective synthesis of amines via reductive amination under transfer hydrogenation conditions

[reaction: see text]. Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.     

Advances in the field of the synthesis of amino derivatives of terpenoids

Information on the synthesis of amino derivatives of monoterpenes by the reduction of oximes by the Leuckart reaction, and by the reductive amination of ketones by amines and nitriles is generalized. The stereochemistry of the amines formed as the result of the above-mentioned reactions is discussed.     

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.     

Knölker's iron complex: an efficient in situ generated catalyst for reductive amination of alkyl aldehydes and amines

An aminated series: a well-defined iron-catalyzed reductive amination reaction of aldehydes and ketones with aliphatic amines using molecular hydrogen is presented. Under mild conditions, good yields for a broad range of alkyl ketones as well as aldehydes were achieved.