Direct and Catalytic Amide Synthesis from Ketones via Transoximation and Beckmann Rearrangement under Mild Conditions

Abstract

The Brønsted acid-catalyzed synthesis of secondary amides from ketones under mild conditions is described via transoximation and Beckmann rearrangement using O-protected oximes as more stable equivalents of explosive O-protected hydroxylamines. This methodology could be applied to highly rearrangement-selective amide synthesis from α-branched alkyl aryl ketones and performed on a 1-g scale. The presence of water is essential for this reaction, and its role was clarified by isotope-labeling experiments.

Sustainable Amidation Reactions – Recent Advances

“…K. Hyodo and co‐workers developed in 2018 a methodology to attain amides 67 and 68 from ketones 65 via transoximation and Beckmann rearrangement using O ‐protected oximes 66 as key intermediates (Scheme ). In order to avoid the use of hazardous reagent such as MSH (( O ‐(mesitylsulfonyl)hydroxylamine)), and undesirable reactions like isomerization, the authors developed a milder approach using stable oxime reagents.…”

Recent Advances in the Development of Catalytic Methods that Construct Medium-Ring Lactams, Partially Saturated Benzazepines and Their Derivatives

“…Hyodo and co-workers developed a method to directly transform ketones into amides by using the Beckmann rearrangement (Scheme 7). 22 The authors targeted the development of a transoximation reaction because this strategy would eliminate the preparation and purification of oximes. While the use of O-(mesitylsulfonyl)hydroxylamine (MSH) enables the synthesis of oximes under mild conditions, 23 it is explosive.…”

The Mechanochemical Beckmann Rearrangement: An Eco-efficient “Cut-and-Paste” Strategy to Design the “Good Old Amide Bond”

“…More recent advances have already addressed, at least in part, these limitations via catalysis with transition metals − or by employing a wide diversity of organic, often toxic, compounds serving as promoters, − such as cyanuric chloride, , propylphosphonic anhydride (T3P), triphosphazene, BOPCl, CDI, − cyclopropenium salts, calcium complexes, sulfonic acid derivatives, − inorganic Lewis acids, , and boronic acids, − among others. − However effective and efficient they may be, most of these synthetic protocols require high temperatures and expensive, volatile, and toxic solvents (2,2,2-trifluoroethanol, hexafluoroisopropanol, CH 3 CN, and DMF) and/or excess of reagents to promote the activation of oximes. All of these concerns pose a serious threat to the application of these methodologies in industrial processes. , …”