Denitrogenative Radical Transacetylation of Amines Using Acetohydrazide in Water at Room Temperature

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

A nonconventional oxidative denitrogenative radical transacetylation method for the chemoselective N-acetylation of primary and secondary aryl/heteroaryl amines using acetohydrazide as a new source acetyl has been discussed. This method, conducted under mild, transition-metal-free conditions in water, offers significant advantages over existing acetylation strategies, which largely rely on harsh reagents such acetic anhydride, chloride, or enzyme catalysts. The process utilizes environmentally friendly reagents, namely, tert-butyl hydroperoxide (TBHP) ammonium iodide (TBAI), to generate radicals through cleavage acetohydrazide, enabling efficient selective wide variety amines, including those bearing other sensitive functional groups. Control experiments with scavengers confirmed situ generation radical, providing strong evidence proposed mechanism. Importantly, this protocol demonstrates excellent scalability successful application synthesis late-stage functionalization pharmaceutical compounds advanced drug intermediates. not only expands toolkit amine but also sustainable scalable approach industrial applications discovery development.

Language: Английский

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Direct Photocatalytic Reductive Amidation of Nitroarenes: A Tandem Reduction–Decarboxylation Approach to Amide Bond Construction

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

We report a photocatalytic strategy for direct amide synthesis from readily available nitroarenes and benzoylformic acids using flavin as an efficient photocatalyst. This one-pot transformation proceeds through tandem reduction-decarboxylation-amidation sequence under mild blue light irradiation. Preliminary mechanistic studies indicated that nitrosoarene N-hydroxyamides could be the key intermediates. The method demonstrates broad substrate scope, excellent functional group tolerance, remarkable operational simplicity, it can conducted ambient atmosphere. Notably, this protocol represents significant advancement in step economy by directly employing diverse nitrogen sources, avoiding need pre-reduced amine

Language: Английский

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Modular synthesis of C₂-symmetric nitrogen-containing polyaromatics via visible light-enabled reductive aza-6π electrocyclization

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(10), P. 2884 - 2890

Published: Jan. 1, 2024

Here, an unprecedented one-step modular construction of C 2 -symmetric N-PACs through reduction/aza-6π electrocyclization was reported and the resultant N-PAC could be converted into a powerful organic photocatalyst.

Language: Английский

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Sulfur-Mediated Decarboxylative Amidation of Cinnamic Acids via C═C Bond Cleavage

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(14), P. 9888 - 9895

Published: June 26, 2024

A new strategy for the synthesis of amides has been developed using sulfur-mediated decarboxylative coupling cinnamic acids with amines via oxidative cleavage C═C bond.

Language: Английский

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Dehydrogenative Conversions of Aldehydes and Amines to Amides Catalyzed by a Nickel(II) Pincer Complex

Catalysts, Journal Year: 2023, Volume and Issue: 13(11), P. 1423 - 1423

Published: Nov. 8, 2023

A C-N cross-coupling approach involving oxidative amidations of aromatic aldehydes in the presence an amide-based nickel(II) pincer catalyst (2) is demonstrated. Upon optimization, quick reaction times (15 min) and ideal temperature (25 °C) were established implemented for conversion 33 different amide products using only 0.2 mol% catalyst. Moderate to good turnover numbers (TONs) obtained secondary benzamide products, moderate TONs tertiary with highest number calculated 4-chloro-N-(3-phenylpropyl)benzamide product (4i, 309). Gas chromatographic–mass spectrometric (GC–MS) analysis also indicates formation alcohols reactions, indicating amidation process. Kinetic studies performed by varying amount catalyst, aldehyde, LiHMDS base, amine substrate determine order each component. Benzaldehyde benzaldehyde-d6 reacted benzylamine, kH/kD ratio was determined understand rate-determining step. Isotope labeling further revealed that deuterium being transferred both alcohol side target product. With help kinetic data UV–visible spectra, a mechanism process via proposed through Ni(I)–Ni(III) pathway.

Language: Английский

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Scalable and Sustainable Reductive Amidation of Nitroarenes, Nitroalkenes, and Nitroalkyls with Acyl Saccharins in Aqueous Media

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

We present a scalable and sustainable methodology for synthesizing N-substituted amides directly from readily available nitroarenes, nitroalkenes, nitroalkyls, acyl saccharin in aqueous media. This eco-friendly atom-efficient approach, which avoids column chromatography, demonstrates excellent functional group compatibility high yield key amide structures. The method's applicability extends to the formal synthesis of Disyprin, bromopyrrole alkaloid, as well amide-based pharmaceuticals agrochemicals. Additionally, we demonstrate its effectiveness multigram-scale paracetamol, alongside solvent recycling. A comprehensive Life Cycle Assessment (LCA; ISO 14044) was conducted evaluate environmental impacts sustainability nine selected Active Pharmaceutical Ingredients (APIs) produced via Non-Amidation Route (NAR) Amidation (AR). study reveals that saccharin-acetylation methods significantly reduce carbon footprints compared NAR is notably carbon-negative resource-efficient. Further impact reduction achievable through recycling adoption low-carbon renewable energy sources, highlighting potential saccharin-based processes substantially mitigate burdens pharmaceutical synthesis.

Language: Английский

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