Amidation Of Amines Research Articles

Aerobic Photooxidative Amidation of Aldehydes and Amines with a Triazine-Based COF

Aerobic Photooxidative Amidation of Aldehydes and Amines with a Triazine-Based COF

Mn3O4 photocatalyzed oxidative amidation of aldehyde and amines for clean synthesis of amides

Amides are widely used in various fields of chemical and pharmaceutical industries. Developing a green and universal amide synthesis method that meets the needs of sustainable chemistry has always been a challenge for amide synthesis. In this paper, a direct and highly selective method for the synthesis of amide was developed under visible light irradiation and room temperature using air as an oxidant. Thanks to the prolongation of the C-H bond (0.1115 nm) and O-H bond (0.1002 nm) during the adsorption of hemiaminal on the Mn3O4 catalyst, and the energy barrier for hemiaminal dehydrogenation (-3.07 eV) is much lower than the energy barrier for dehydration (4.84 eV), thus the formation of imines is suppressed, resulting in highly selective clean production of amides with H2O as byproduct. Therefore, this clean and effective method for obtaining amides is one of the ideal alternative solutions for currently known methods.

I2-Catalyzed Oxidative Acylation of Tertiary Amines via C–N Bond Cleavage

AbstractThe development of catalysts for the amidation of tertiary amines with acyl chlorides through oxidative C–N bond cleavage is rather challenging. By employing iodine as the catalyst, a broad range of aromatic acyl chlorides and tertiary amines are efficiently converted into amides in good yields under mild conditions. A plausible mechanistic pathway is proposed for this transformation and is supported by appropriate control experiments.

Efficient amidation of weak amines: synthesis, chiral separation by SFC, and antimicrobial activity of N-(9,10-dioxo-9,10-dihydroanthracen-1-yl) carboxamide.

An effective and straightforward method for the synthesis of 1-aminoanthracene-9,10-dione carboxamides by coupling a weakly reactive amine, 1-aminoanthracene-9,10-dione, and sterically hindered carboxylic acids was achieved using COMU as the coupling agent. Furthermore, making use of the advantages associated with the super-critical fluid chromatography (SFC) technique, a simplified and straightforward method for the chiral separation of optically active amide derivatives from the impurities associated with the reaction mixture, in a single step, was demonstrated. The antimicrobial activity of selected 1-aminoanthracene-9,10-dione carboxamides was studied. Advanced NMR and other spectral techniques were used for the thorough characterization of all the compounds. This study provides a general and simplified method for coupling a weak amine with a sterically hindered acid using COMU as a coupling agent, and demonstrates the separation of optically pure compounds from reaction related impurities in a single step using SFC, and identification of amide derivatives of 1-aminoanthracene-9,10-dione as potential antimicrobial agents.

Mechanistic study of NHC-catalyzed oxidative N vs. O chemoselective acylation of aldehydes with alkanolamines

We studied the mechanism of NHC-catalyzed oxidative amidation of aryl aldehydes and amines, the sources of chemoselectivity, and the role of additives through DFT calculations.

Boric Acid-Grafted Biochar (BoAB) for the Direct Amidation of Carboxylic Acids and Amines

Amidation is a key step in the development of numerous industrially and biologically relevant molecules, yet conventional methods often suffer from inefficiency and poor atom economy. In response, we introduce...

Less Is More: N(BOH)2 Configuration Exhibits Higher Reactivity than the B3NO2 Heterocycle in Catalytic Dehydrative Amide Formation.

Diboron substructures have emerged as a promising scaffold for the catalytic dehydrative amidation of carboxylic acids and amines. This Letter describes the design, synthesis, and evaluation of the first isolable N(BOH)2 compound as an amidation catalyst. The new catalyst outperforms the previously reported B3NO2 heterocycle catalyst, with respect to turnover frequency, albeit the former gradually decomposes upon exposure to amines. This work opens up an avenue for designing a better catalyst for direct amidation.

Direct intermolecular C(sp3)–H amidation with dioxazolones via synergistic decatungstate anion photocatalysis and nickel catalysis: A combined experimental and computational study

The direct C(sp3)–H amidation is a highly desirable but challenging approach to construct C(sp3)–N bonds. Herein, we describe a new strategy combining photoredox-mediated hydrogen atom transfer (HAT) and transition-metal catalysis for intermolecular C(sp3)–H amidation of unactivated alkanes, ketones, ethers, amines, and aldehydes with dioxazolones. This protocol, employing synergistic tetrabutylammonium decatungstate (TBADT) anion photocatalysis and nickel catalysis, provides a practical approach to realize a direct intermolecular C(sp3)–H amidation with useful reactivity and site selectivity under mild conditions, which may be applied to the late-stage modification of complex molecules. A combined experimental and computational mechanistic study implies the formation of a key [W10O32]4-–Ni(I) species under irradiation of UV-A. The unusual cooperative roles of [W10O32]4- anion and Ni(I) moiety are suggested in generating a C-centered radical from C(sp3)–H bond and an amido group from dioxazolone, respectively. Subsequently, the formation of a [W10O32]4-–Ni(III) complex followed by a reductive elimination step is proposed to afford the desired amidation product.

Ruthenium-Catalyzed Direct Asymmetric Reductive Amination of α-Keto Amides with Ammonium Salts

Ruthenium-Catalyzed Direct Asymmetric Reductive Amination of α-Keto Amides with Ammonium Salts

Mechanistic Studies on the Synthesis of Pyrrolidines and Piperidines via Copper-Catalyzed Intramolecular C-H Amination.

We have recently developed a method for the synthesis of pyrrolidines and piperidines via intramolecular C–H amination of N-fluoride amides using [TpxCuL] complexes as precatalysts [Tpx = tris(pyrazolyl)borate ligand and L = THF or CH3CN]. Herein, we report mechanistic studies on this transformation, which includes the isolation and structural characterization of a fluorinated copper(II) complex, [(TpiPr2OH)CuF] [TpiPr = hydrotris(3,5-diisopropylpyrazolyl)borate], pertinent to the mechanistic pathway. The effects of the nature of the Tpx ligand in the copper catalyst as well as of the halide in the N–X amides employed as reactants have been investigated both from experimental and computational perspectives.

Highly Enantioselective Synthesis of N-Unprotected Unnatural α-Amino Acid Derivatives by Ruthenium-Catalyzed Direct Asymmetric Reductive Amination.

An unprecedented highly enantioselective Ru-catalyzed direct asymmetric reductive amination of α-keto amides with ammonium salts has been disclosed, efficiently offering valuable enantioenriched N-unprotected unnatural α-amino acid derivatives bearing a broad range of aryl or alkyl α-substituents. This protocol features easily accessible substrates, good functional-group tolerance and excellent enantiocontrol, making it a good complementary approach to the known methods. Moreover, this method is also applicable to the preparation of N-unprotected unnatural α-amino acid derivatives containing an additional stereogenic center at the β-position through a dynamic kinetic resolution (DKR) process. Convenient transformations of the obtained products into chiral N-unprotected unnatural α-amino acids, drug intermediates, peptides, and organocatalysts/ligands further showcase the utility of this method.

Synthesis and characterization of rare earth/lithium complexes stabilized by ethylenediamine-bridged bis(phenolate) ligands and their activity in catalyzing amidation reactions

Rare earth/lithium complexes stabilized by ethylenediamine-bridged bis(phenolate) ligands have been synthesized and characterized. In addition to five rare earth/lithium amides isolated as major complexes, two other rare earth/lithium complexes bearing two phenolate ligands were also isolated. The activities of rare earth/lithium amides in catalyzing the amidation of aldehydes and amines were studied, which revealed that the yttrium/lithium complex was highly active for a wide range of substrates, generating 58 examples of amides in 42-99% yields under mild conditions (i.e., room temperature, 3-hour reaction time, additive-free). More importantly, this is the first example of rare earth-based catalysts capable of catalyzing the amidation of primary aliphatic amines.

Ligand Enabled Pd(II)-Catalyzed γ-C(sp3)-H Lactamization of Native Amides.

γ-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular γ-C-H amination of aliphatic amides would allow for the direct construction of valuable γ-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed γ-C(sp3)-H lactamization of amino acid derived native amides, providing the convenient synthesis of γ-lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of N-acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign tert-butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

Convenient Synthesis of Benziodazolone: New Reagents for Direct Esterification of Alcohols and Amidation of Amines.

Hypervalent iodine heterocycles represent one of the important classes of hypervalent iodine reagents with many applications in organic synthesis. This paper reports a simple and convenient synthesis of benziodazolones by the reaction of readily available iodobenzamides with m-chloroperoxybenzoic acid in acetonitrile at room temperature. The structure of one of these new iodine heterocycles was confirmed by X-ray analysis. In combination with PPh3 and pyridine, these benziodazolones can smoothly react with alcohols or amines to produce the corresponding esters or amides of 3-chlorobenzoic acid, respectively. It was found that the novel benziodazolone reagent reacts more efficiently than the analogous benziodoxolone reagent in this esterification.

Photochemical Regioselective C(sp3)-H Amination of Amides Using N-Haloimides.

A metal-free regioselective C(sp3)-H amination of amides using N-haloimides in the presence of lithium tert-butoxide and visible light is presented herein. This photoexcited approach is straightforward, and it aminates a wide variety of amides under mild conditions without the use of photocatalysts, external radical initiators, or oxidants. A halogen-bonded intermediate between the tert-butoxide base and the N-haloimide is proposed to be responsible for the increased photoreactivity. Calculations show that the formation of this electron donor-acceptor complex presents an exergonic energy profile.

Discovery and Design of Family VIII Carboxylesterases as Highly Efficient Acyltransferases.

Promiscuous acyltransferase activity is the ability of certain hydrolases to preferentially catalyze acyl transfer over hydrolysis, even in bulk water. However, poor enantioselectivity, low transfer efficiency, significant product hydrolysis, and limited substrate scope represent considerable drawbacks for their application. By activity‐based screening of several hydrolases, we identified the family VIII carboxylesterase, EstCE1, as an unprecedentedly efficient acyltransferase. EstCE1 catalyzes the irreversible amidation and carbamoylation of amines in water, which enabled the synthesis of the drug moclobemide from methyl 4‐chlorobenzoate and 4‐(2‐aminoethyl)morpholine (ca. 20 % conversion). We solved the crystal structure of EstCE1 and detailed structure–function analysis revealed a three‐amino acid motif important for promiscuous acyltransferase activity. Introducing this motif into an esterase without acetyltransferase activity transformed a “hydrolase” into an “acyltransferase”.

Porous [Ru(bpy)3]2+-Cored Metallosupramolecular Polymers: Preparation and Recyclable Photocatalysis for the Formation of Amides and 2-Diazo-2-phenylacetates

A covalently bonded three-dimensional [Ru(bpy)3]2+-cored metallosupramolecular polymer (MSP-CB[8]-c) has been prepared from a noncovalently bonded metallosupramolecular polymer (MSP-CB[8]-nc) through cucurbit[8]uril (CB[8])-promoted [2 + 2] photodimerization of the ethylene units. Both MSPs function well as heterogeneous photocatalysts for visible light-induced amidation of aromatic amines with potassium thioacetate and the C–H diazomethylation of arenes with a benziodoxolone, and MSP-CB[8]-c exhibits increased catalytic activity than MSP-CB[8]-nc or a CB[8]-free metallosupramolecular polymer (MSP-c). For both kinds of reactions, the catalytic activity of the [Ru(bpy)3]2+ unit of MSP is comparable with that obtained by homogeneous prototypic Ru(bpy)3Cl2 or Ru(bpy)3(PF6)2 due to its porosity but allows for remarkable recyclability and can be reused 12 times while maintaining a considerable activity.

Cu-Catalyzed Direct Amination of Cyclic Amides via C-OH Bond Activation Using DMF.

Herein, we describe a Cu-catalyzed approach to directly accessing aromatic heterocyclic amines from cyclic amides. The most-reported methods for cyclic amide conversions to aromatic heterocyclic amines use an activating group, such as a halogen atom or a trifluoromethane sulfonyl group. However, subsequent elimination of activating groups during the amination process results in significant waste. This copper-catalyzed direct amination of cyclic amides in DMF forms aromatic heterocyclic amines with environmental friendliness and readily available reagents. A plausible radical mechanism has been proposed for the reaction. Meanwhile, the coordinating effect of the N1 atom is key to the success of this reaction, which provides assistance to the copper ions for the activation and amination of C-O bonds.

Oxidative Amidation of Amines in Tandem with Transamidation: ARoute to Amides Using Visible-Light Energy.

A methodology is reported for preparing amides using amines as an acyl source. The protocol involves the visible-light-promoted oxidative amidation of amines with pyrazole to synthesize N-acyl pyrazoles followed by transamidation. By combining photoredox catalysis with oxoammonium cations in the presence of sodium persulfate as a terminal oxidant, the N-acyl pyrazoles could be prepared efficiently and effectively using blue LEDs. The transamidation step was performed without the need to purify the N-acyl pyrazole intermediate, and a range of amides were generated in good to excellent yields.

Electrochemical Synthesis of α-Ketoamides under Catalyst-, Oxidant-, and Electrolyte-Free Conditions.

A catalyst-, oxidant-, electrolyte-free method for the preparation of α-ketoamides through the direct electrochemical amidation of α-ketoaldehydes and amines with innocuous hydrogen as the sole byproduct at ambient temperature was developed. The present reaction features clean and mild conditions, excellent functional-group tolerance, and high atom economy and scalability, enabling facile applications in pharmaceutical chemistry.