Oxidative Amidation Research Articles

Oxidative Amidation of Ferrocenyl Aldehydes with Amines Catalyzed by Chalcogenised Fe3Se2(CO)9 Cluster: Direct Transformation of Aldehyde to Amides.

With the interest and knowing the importance of ferrocenyl conjugates, a direct amidation of ferrocenyl aldehyde has been developed under feasible conditions. Varieties of amines has been oxidatively coupled with ferrocene aldehyde in the presence of highly economical and robustly stable iron chalcogenide ironcarbonyl clusters [Fe3E2(CO)9, E= S, Se, and Te] and TBHP. The reaction worked in greener solvent water at a moderate temperature of 70 °C and the ferrocenyl-amides in just 30 minutes. All the varieties of amines were found to be well tolerated for the present method, and due to the high medicinal importance of ferrocenyl-amides, sole focus of this report was concentrates on the synthesis of various new ferrocenyl-amides in good to excellent amounts.

Scale-up of Sodium Persulfate Mediated, Nitroxide Catalyzed Oxidative Functionalization Reactions.

Oxidation is a valuable tool in preparative organic chemistry. Oxoammonium salts and nitroxides have proven valuable as reagents and catalysts in this endeavor. The objective of this study is to scale up the oxidative amidation, ester formation, and nitrile formation using nitroxide as an organocatalyst. Oxidative functionalization reactions were scaled from the 1 mmol to the 1 mole level. Sodium persulfate was used as the primary oxidant, and a nitroxide was employed as a catalyst. The products of the reactions were isolated in analytically pure form by extraction with no need for column chromatography. The oxidative amidation and esterification of aldehydes can be scaled up from 1 mmol to 1 mole effectively, with comparable product yields being obtained at each increment. This work shows that conditions developed on a small scale can be transferred to a larger scale without reoptimization. The oxidative functionalization of aldehydes to prepare nitriles is not amenable to direct scale-up due to the concomitant formation of significant quantities of the corresponding carboxylic acid, thereby compromising the product yield. Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1 mole level.

Naphthalene Monoanhydride and Perylene Composites for Efficient Photocatalytic Hydrogen Evolution and Metal-Free Heterogeneous Oxidative Amidation.

This study explores the synthesis of two visible light active organic chromophore-based composites using naphthalene monoanhydride (Np) and 1,7-dibromoperylene monoanhydride diester (PMDE). These chromophores feature favorable optical and electronic properties and polyaromatic skeletons with anhydride functionalities that facilitate π-π interactions between the chromophore and polymeric carbon nitride (CN) or covalent connections of chromophores with NH2 groups of CN. Accordingly, heterogeneous chromophore-CN composite photocatalysts namely, Np/CN(c) and PMDE/CN(c) were prepared by adopting in situ calcination (c) and composites Np/CN(a) and PMDE/CN(a) were prepared by ex situ physical adsorption (a) methods. In situ prepared Np/CN(c) and PMDE/CN(c) composites exhibited H2 evolution rates (HER) of 1069 and 705 μmol h-1 g-1, respectively, which are significantly higher than ex situ Np/CN(a) and PMDE/CN(a) composites with HER of 465 and 252 μmol h-1 g-1, respectively. These rates are 10, 7, 4.8, and 2.5 times higher than the bulk-CN, indicating the potential of these composites for efficient photocatalytic H2 evolution. Surface area normalized HER enhancements were 3.8, 5.3, 6.6, and 4.2 times higher for Np/CN(c), PMDE/CN(c), Np/CN(a), and PMDE/CN(a) respectively compared to bulk-CN. These composite photocatalysts exhibited excellent stabilities under prolonged photoirradiation, with H2 evolution consistently increasing with the light exposure time. Additionally, these metal-free heterogeneous composites demonstrated efficient photocatalytic activities towards oxidative amidation of aromatic aldehydes, with up to 80% product yields, establishing the prospects of combining homogeneous and heterogeneous entities in a metal-free active material in solar energy harvesting.

Direct Synthesis of Sugar Amides by Aerobic One-Pot Oxidative Amidation of Unprotected Carbohydrates

Direct Synthesis of Sugar Amides by Aerobic One-Pot Oxidative Amidation of Unprotected Carbohydrates

Single‐Pot Synthesis and Optimization of CCF@GO Nanocatalyst for Efficient Direct Oxidative Amidation of Carboxylic Acids and N,N‐Dialkylformamides

ABSTRACTIn this study, an efficient catalytic protocol using CuCoFe2O4@GO (CCF@GO) for the synthesis of amide bond (−CONH−) via direct coupling of carboxylic acids and N,N‐dialkylformamides is presented. The CCF@GO nanocatalyst has been synthesized via a single‐pot solvothermal method, by changing the proportions of copper and cobalt (1:1, 1:3, and 3:1). Catalyst screening, employing a model reaction with benzoic acid and dimethylformamide (DMF), revealed that the 1:1 proportion of CCF@GO catalyst exhibited excellent efficiency, achieving a high conversion (98%) towards amide formation. The enhanced catalytic efficiency observed in CCF@GO catalysts can be ascribed to the uniform distribution of active copper and cobalt species on the graphene oxide support, which possesses a high surface area. Optimization of the reaction was conducted by varying parameters such as temperature, solvent, catalyst loading, and oxidant. The prepared catalyst was characterized using various analytical techniques including XRD, FTIR, XPS, SEM, EDX mapping, and TEM. Furthermore, this heterogeneous nanocatalyst demonstrated recoverability using an external magnet and reused up to five times with just a modest loss of catalytic performance.

Synthesis of α-ketoamides via oxidative amidation of diazo compounds with O-benzoyl hydroxylamines as nitrogen source and the oxidant.

A simple, efficient method has been described for the construction of an array of α-ketoamides from readily available O-benzoyl hydroxylamines and diazo compounds as starting materials. There was a combined use of CuI as a catalyst and H2O as the oxygen source. The investigation reveals that the O-benzoyl hydroxylamines serve a dual role as both an amine source and the oxidant in this mechanism, thereby obviating the need for additional oxidants in the transformation process. This methodology could give a wider range of products in good to excellent yields for most substrates, and thus, we provide a new idea for the synthesis of α-ketoamides.

Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis.

Berberine bridge enzyme-like oxidases are often involved in natural product biosynthesis and are seen as essential enzymes for the generation of intricate pharmacophores. These oxidases have the ability to transfer a hydride atom to the FAD cofactor, which enables complex substrate modifications and rearrangements including (intramolecular) cyclizations, carbon-carbon bond formations, and nucleophilic additions. Despite the diverse range of activities, the mechanistic details of these reactions often remain incompletely understood. In this Review, we delve into the complexity that BBE-like oxidases from bacteria, fungal, and plant origins exhibit by providing an overview of the shared catalytic features and emphasizing the different reactivities. We propose four generalized modes of action by which BBE-like oxidases enable the synthesis of natural products, ranging from the classic alcohol oxidation reactions to less common amine and amide oxidation reactions. Exploring the mechanisms utilized by nature to produce its vast array of natural products is a subject of considerable interest and can lead to the discovery of unique biochemical activities.

Regioselective α-Phosphonylation of Unprotected Alicyclic Amines.

Unprotected alicyclic amines undergo α-C-H bond phosphonylation via a two-stage one-pot process involving the oxidation of amine-derived lithium amides with simple ketone oxidants, generating transient imines which are then captured with phosphites or phosphine oxides. Amines with an existing α-substituent undergo regioselective α'-phosphonylation. Amine α-arylation and α'-phosphonylation can be combined, generating a difunctionalized product in a single operation.

One-Pot Oxidative Amidation of Aldehydes via the Generation of Nitrile Imine Intermediates.

A one-pot procedure for the oxidative amidation of aldehydes via the in situ generation of reactive nitrile imine (NI) intermediates has been developed. Distinct from our progenitor processes, mechanistic and control experiments revealed that the NI undergoes rapid oxidation to an acyl diazene species, which then facilitates N-acylation of an amine. A range of substrates have been explored, including application in the synthesis of pharmaceutically relevant compounds.

Iron Photocatalysis Applied to Oxidative Amidation of Aldehydes with NaCl

AbstractA synthesis of amides from aldehydes promoted by the photoactive complex of Fe2SO4 with 2‐picolinic acid, NaCl as a chlorine source, and Na2S2O8 as a benign oxidant is reported. The reaction is mediated by visible light and is carried out at room temperature in the absence of additives. Fe2SO4 is a readily available earth‐abundant metal (EAMs) salt, which does not need to be prepared and is environmentally sustainable. Both aliphatic and aromatic aldehydes and mono‐ and disubstituted amines have been investigated for this transformation. This study opens intriguing perspectives for extending the application of photoactive complex iron salts toward halogenation processes as well as for C−H activation reactions and contributes to the field of earth‐abundant metal based catalysis.

Oxidative Amidation of Aldehydes with an N-Doped Carbon-Supported Ni Catalyst

Oxidative Amidation of Aldehydes with an N-Doped Carbon-Supported Ni Catalyst

Copper‐Promoted Oxidative Amidation of Imines: A Facile Route to Amides

Copper‐Promoted Oxidative Amidation of Imines: A Facile Route to Amides

Oxidative amidation of aldehydes with amine in a mixture of choline chloride and aluminium nitrate as oxidant and solvent

Amides can be synthesized directly from aldehydes and amines in high yield using a catalyst. The reaction, involving aldehydes and amines, was carried out in a mixture containing choline chloride and aluminum nitrate as a solvent and a catalyst to produce amides. Such catalyst was far more effective compared to other current catalytic systems. The reaction consistently gave exceptionally remarkable results for various aldehyde and amine derivatives under the specified reaction conditions. This method offers several advantages, including easy separation of products, efficiency, environmentally safe nature of the solvent, and elimination of expensive and hazardous catalysts. These features emphasize the importance of such groundbreaking reactions. Due to the significant polar characteristics and insolubility of the resulting products in water, the addition of water into the reaction mixture facilitates the easy separation of the products from the reaction medium. Consequently, this particular ionic liquid method provides a simple route for the synthesis of these important compounds.

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.

Anodic Oxidation of Aliphatic and Aromatic Amides, Bisamides and Related Derivatives

AbstractThe current comprehensive review covers four main parts, of which some are presented in the form of a personal account. 1. Anodic oxidation of a) N‐alkyl and N,N‐diallyl carbonyl moieties, b) Azacycloalkyl amides and the effect of ring‐size on the outcome, c) Lactams, d) Sulfonamides, and e) The effect of a substituent R attached to carbonyl (N−CO−R) or sulfonamides (N−SO2R) on their oxidation potentials. 2. Anodic oxidation of aromatic amides, in particular of type Ph2CHCONHAr, lacking hydrogen(s) at the α‐position to nitrogen. They undergo three types of bond‐cleavage, yielding a variety of fragmentation products. 3. a) Anodic oxidation of symmetrical bisamides of type ZCONH(CH2)nNHCOZ (Z=Me, Ph, Ar; n=2–4) under constant current electrolysis, in methanol. For n=3, 4 they afford mostly mono‐ and dimethoxylation products. For n=2 they undergo ′CH2−CH2′ bond cleavage to yield fragmentation products. b) Anodic oxidation of symmetrical bisamides of type ArCONH(CH2)2NHCOAr under controlled potential electrolysis, in acetonitrile, leads to gem‐unsymmetrical bisamides of type ArCONHCH2NHCOMe as the major product, in fair yields. 4. Utilization of the anodic process in organic synthesis to form C−C bonds by both intra‐ and inetrmolecular processes; as well as C−O and C−N bonds for generating heterocycles.

IMesCuCl/TBHP system for aqueous oxidative amidation: Synthesis of new amide derivatives as EGFR targeting anti-breast cancer agents and computational studies

A base free and aqueous synthesis of some new 1,4-benzoxazinone-tetrazole containing amides via tert‑butyl hydroperoxide (TBHP) mediated oxidative coupling of 2-(5-(2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)ethyl)-2H-tetrazol-2-yl)acetaldehyde (10) with anilines (11a-n) under (1,3-dimesityl-2,3-dihydro-1H-imidazol-2-yl)copper(I) chloride (IMesCuCl) catalysis was reported herein for the first time. All these compounds (12a-n) were screened for their in vitro anti-breast cancer activity against two human breast cancer cell lines (MDA-MB-231 and MCF-7). Out of all, compound 12g showed greater activity than the Erlotinib on two cell lines with IC50 values in the range of 4.12–7.03 μg/mL. As well, compounds 12a and 12c showed greater activity than the Erlotinib on MCF-7 with IC50 values <4.5 μg/mL. The tyrosine kinase Epidermal Growth Factor Receptor (EGFR) inhibition studies revealed that compound 12g showed almost similar potency (IC50 = 0.47 μM) with the Erlotinib (IC50 = 0.41μM). Molecular docking studies revealed that compounds 12a, 12c and 12g showed encouraging binding energies and inhibition constants on EGFR (PDB ID-4HJO) than the Erlotinib. Finally, the most potent compound 12g was characterized by density functional theory (DFT) with B3LYP/6–311++ G (d, p) basis set. The structural parameters were obtained from geometry optimization. Molecular electrostatic potential (MEP) and highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gap and Mulliken atomic charges were calculated.

Pd NPs decorated on crosslinked sodium alginate modified iron-based metal-organic framework Fe(BTC) as a green multifunctional catalyst for the oxidative amidation.

The primary objective of this investigation was to develop a new nanocatalyst that could produce amides by oxidative amidation of benzyl alcohol, thereby reducing its environmental harm. To achieve this, Pd nanoparticle-immobilized crosslinked sodium alginate-modified iron-based metal-organic framework Fe(BTC) (Fe(BTC)@SA/ED/Pd), with excellent activity and selectivity in modified oxidative amidation of benzyl alcohol with amines, has been described. Crosslinked sodium alginate was modified on iron-based metal-organic framework Fe(BTC). It is worth noting that Pd nanoparticles were immobilized for the first time on a novel nanocomposite based on the Fe(BTC) MOF and crosslinked sodium alginate for tandem oxidative amidation to improve the eco-friendliness and economic efficiency of the process. The synergic effects of Fe(BTC), sodium alginate, and Pd NPs are important factors influencing the catalytic activity. Easy and green synthesis methods, availability of materials, high Pd loading, available catalytic sites, high surface area, high selectivity, and simple separation from the reaction medium are effective properties in catalytic activity.

Unified and green oxidation of amides and aldehydes for the Hofmann and Curtius rearrangements

The oxone–halide green oxidation system is extended to the oxidation of primary amides and aromatic aldehydes (with sodium azide) to generate N-haloamide and acyl azides, respectively, for subsequent Hofmann and Curtius rearrangements.

C-N cleavage of secondary amide to access primary amide by a Co(II)/Oxone oxidation system.

Cleavage of the C-N bond of a secondary amide could provide alternative access to primary amides; however, this strategy remains challenging due to oxidation resistance of the amide. Herein, we employed the cobalt(II)/Oxone catalytic system, one of the advanced oxidation processes (AOPs), to make it available to break the strong C-N bond of various secondary (sulfon)amides, especially those bearing electron-poor or ortho-substituted N-arenes, en route to desirable primary (sulfon)amides. Control experiments showed that it was probably not the generally-considered persulfate anion radical in the cobalt/peroxymonosulfate (Co/PMS) system but the proposed high-valent cobalt-oxo intermediate that should be the major active species for the initial N-H oxidation of N-aryl amides. In the case of N-alkylated secondary amides, the α-C-H bond, rather than the N-H bond, should be oxidized first by both the reactive radicals and high-valent cobalt-oxo species. This work not only establishes an efficient method for removing the N-substituents of secondary amides at low cost, with readily available and eco-friendly reagents, but also demonstrates further synthetic application and provides more insight into intermediates for metal-based AOPs in environmental remediation.

Selective α-oxidation of amides via visible-light-driven iron catalysis.

Hydroxyl radicals (˙OH) as one of the highly reactive species can react unselectively with a wide range of chemicals. The ˙OH radicals are typically generated under harsh conditions. Herein, we report hydroxyl radical-induced selective N-α C(sp3)-H bond oxidation of amides under greener and mild conditions via an Fe(NO3)3·9H2O catalyst inner sphere pathway upon irradiation with a 30 W blue LED light strip (λ = 455 nm) using NaBrO3 as the oxidant. This protocol exhibited high chemoselectivity and excellent functional group tolerance. A preliminary mechanism investigation demonstrated that the iron catalyst afforded hydroxyl radicals via the visible-light-induced homolysis (VLIH) of iron complexes followed by a hydrogen atom transfer (HAT) process to realize this transformation.