Oxidative Amidation Research Articles

Cleavage of 1,3-dicarbonyls through oxidative amidation.

A mild and convenient protocol for the oxidative cleavage of 1,3-diketone compounds is described. Under metal-free conditions, the method converts the 1,3-dicarbonyls into amides when treated with (nBu4N)N3 and iodine in the presence of an amine at room temperature. Using this method, a range of 1,3-dicarbonyls with various structural motifs including sterically demanding substituents and ordinary functional groups were easily fragmented, and it is demonstrated that cyclic 1,3-dicarbonyls can be directly transformed into acyclic diamides through ring-opening. Initial mechanistic studies show that diazidation of the enol form is followed by nucleophilic substitution with the amine.

Oxidative amidation of benzaldehydes and benzylamines withN-substituted formamides over a Co/Al hydrotalcite-derived catalyst

A highly efficient synthetic strategy for amidesviaoxidative amidation of benzaldehydes or benzylamines withN-substituted formamides has been developed using cobalt based heterogeneous catalyst.

Copper-catalyzed aerobic oxidative intramolecular amidation of 2-aminophenylacetylenes: a domino process for the synthesis of isatin

A novel CuI-catalyzed oxidative amidation of 2-aminophenylacetylenes leading to the formation of isatins by using open air as an oxygen source has been developed. The reaction proceeded smoothly and provided a variety of isatin derivatives in good yields.

Aerobic oxidative decyanation–amidation of arylacetonitriles with urea as a nitrogen source

An iron-catalyzed aerobic oxidative amidation of aryl acetonitriles to afford amides is achieved using urea as a convenient nitrogen source.

Cu-catalyzed aerobic oxidative C–CN bond cleavage of benzyl cyanide for the synthesis of primary amides

Cu-catalyzed oxidative amidation of benzyl cyanide for primary amides is successfully developed. Using readily available NH4Cl and Cu/O2 catalytic oxidation system offers new opportunities for C–CN bond cleavage and primary amides bond formation.

Copper-catalyzed one-pot oxidative amidation between methylarenes and amines

A method for the synthesis of amides through direct one-pot oxidative amidation of methylarenes with amines catalyzed by copper has been developed.

1,3-Dibromo-5,5-dimethylhydantoin mediated oxidative amidation of terminal alkenes in water.

A variety of terminal alkenes were converted to the corresponding amides in yields of 25 to 86% in water via treatment with 1,3-dibromo-5,5-dimethylhydantoin, followed by reaction with molecular iodine and aq. NH3 (or amine) in one pot. This metal- and organic solvent-free protocol is not only suitable for styrene derivatives, but also, for the first time, works well on terminal aliphatic alkenes.

An efficient and mild oxidative amidation of aldehydes using B(C6F5)3 as a catalyst and biological evaluation of the products as potential antimicrobial agents

A mild and efficient protocol for oxidative amidation of diverse aldehydes with amines was developed to generate the corresponding amides in good to excellent yields.

Copper-catalyzed oxidative amidation of α,β-unsaturated ketones via selective C–H or C–C bond cleavage

The copper-catalyzed oxidative amidation of α,β-unsaturated ketones with N-fluorobenzenesulfonimide (NFSI) via a highly regioselective cleavage of C(CO)–C(vinyl) or C(vinyl)–H bonds of ketones has been achieved.

Facile synthesis of N-acyl 2-aminobenzothiazoles by NHC-catalyzed direct oxidative amidation of aldehydes.

A mild, general, and high yielding synthesis of N-acyl 2-aminobenzothiazoles has been demonstrated by N-heterocyclic carbene (NHC)-organocatalyzed direct amidation of aldehydes with 2-aminobenzothiazoles proceeding via acyl azolium intermediates. The carbene generated from the triazolium salt under oxidative conditions was the key for the success of this reaction. The method was subsequently applied to the synthesis of various biologically important N-acyl 2-aminobenzothiazoles.

Oxidative functionalisation of alcohols and aldehydes via the merger of oxoammonium cations and photoredox catalysis.

We present a new paradigm for nitroxyl-mediated processes via the merger of oxoammonium cation-mediated oxidation with visible-light photoredox catalysis. The integration of these two forms of catalysis has been realised for the oxidative amidation of aldehydes, furnishing N-acylated heterocycles. Extension of this process to the oxidative amidation of alcohols via the intermediacy of an aldehyde was successfully pursued, thus proffering a general oxidation platform. The activated amides synthesised here are excellent synthetic handles for acylation.

Iodine‐Catalyzed Formation of Amide Bond: Efficient Strategy for the Synthesis of Aromatic Primary Amides

AbstractA practical and efficient methodology for the synthesis of aromatic primary amides by reaction of benzylic alcohols and aqueous ammonia in the presence of an I2/TBHP system in acetonitrile was developed. This oxidative amidation proceeded smoothly at ambient temperature and tolerated a variety of functional groups. A wide range of aromatic primary amides were obtained in moderate to high yields. Preliminary kinetic studies and a possible mechanism of the oxidative amidation reaction were also discussed.

ChemInform Abstract: Room Temperature Copper‐Catalyzed Oxidative Amidation of Terminal Alkynes for the Synthesis of α‐Ketoamides Using O‐Benzoyl Hydroxylamines as Aminating Reagent and Oxidant.

AbstractThe title reaction only applies to terminal aryl alkynes and tertiary amines.

Kinetic Study of the Reaction of the Phthalimide-N-oxyl Radical with Amides: Structural and Medium Effects on the Hydrogen Atom Transfer Reactivity and Selectivity.

A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of secondary N-(4-X-benzyl)acetamides and tertiary amides to the phthalimide-N-oxyl radical (PINO) has been carried out. The results indicate that HAT is strongly influenced by structural and medium effects; in particular, the addition of Brønsted and Lewis acids determines a significant deactivation of C-H bonds α to the amide nitrogen of these substrates. Thus, by changing the reaction medium, it is possible to carefully control the regioselectivity of the aerobic oxidation of amides catalyzed by N-hydroxyphthalimide, widening the synthetic versatility of this process.

Rhodium-Catalyzed Oxidative Amidation of Sterically Hindered Aldehydes and Alcohols

A rhodium-catalyzed oxidative amidation reaction has been developed with sterically hindered aldehydes and alcohols for the synthesis of amides containing a quaternary carbon at the α position. A variety of amine nucleophiles, both aliphatic and aromatic, are employed and afford the corresponding amides in good to excellent yields. Finally, mechanistic studies are performed to gain insight into both catalytic cycles.

An efficient, eco-friendly and sustainable tandem oxidative amidation of alcohols with amines catalyzed by heteropolyanion-based ionic liquids via a bifunctional catalysis process

An efficient, eco-friendly and sustainable method for the tandem oxidative amidation of alcohols with amines has been reported. Using heteropolyanion-based ionic liquids as the catalyst and tert-butyl hydroperoxide as the oxidant, this amidation reaction is operationally straightforward and provides a series of primary, secondary and tertiary amides derivatives in moderate to good yields. Solvent-free media, microwave-promoted conditions and reusability of catalysts are the main highlights. Further, the proposed bifunctional catalysis mechanistic pathway has been briefly investigated in this report.

ChemInform Abstract: Sterically Demanding Oxidative Amidation of α‐Substituted Malononitriles with Amines Using O2.

AbstractSterically and electronically demanding 1,1‐dicyanoalkanes react in a practical chemoselective manner with functionalized non‐chiral or chiral amines and molecular oxygen to provide various amides, including amino acid derivatives in high yields.

Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols

A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl2, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pKa of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.

Oxidative Amidation of Aromatic Aldehydes on Silver/Graphitic Carbon Nitride

Oxidative Amidation of Aromatic Aldehydes on Silver/Graphitic Carbon Nitride

Metal–Organic Framework Based on Copper and Carboxylate‐Imidazole as Robust and Effective Catalyst in the Oxidative Amidation of Carboxylic Acids and Formamides

A metal–organic framework (MOF) based on copper and 1,3‐bis(carboxymethyl)imidazole (bcmim) was prepared on a gram scale by using a precipitation method at room temperature. The Cu(bcmim)2 MOF was shown to be an efficient catalyst for the preparation of amides through an oxidative coupling between carboxylic acids and formamides in the presence of an oxidant, such as tert‐butyl hydroperoxide (TBHP). The method for the preparation of the amides is robust regardless of the carboxylic acid and gives good conversions with good selectivity. The heterogeneous catalyst was recovered unaltered after the reaction, was easily separated from the reaction mixture, and subsequently reactivated by suitable treatment. Moreover, the coupling reaction was scaled up to a gram scale, which allowed for the preparation of valuable products, such as fatty acid amides (i.e., 1‐palmitoylpiperidine).