Efficient Iodine-Mediated Beckmann Rearrangement of Ketoximes to Amides under Mild Neutral Conditions

Abstract

Aryl ketoximes readily underwent Beckmann rearrangement to give N-substituted amides in excellent yields on electrophilic activation by elemental iodine in anhydrous acetonitrile under reflux. The main advantages of this environmentally friendly protocol include a high selectivity as a result of the absence of any accompanying deprotection to form the parent ketones as byproducts, mild neutral conditions, procedural simplicity, and particularly ease of isolation of the products.

2,5‐Diamide‐Substituted Five‐Membered Heterocycles: Challenging Molecular Synthons

“…Different possible routes are amidation cross-coupling reactions, [28][29][30][31][32] Beckmann rearrangement of ketoximes, [33][34][35][36] formation of azido intermediates convertible into amide derivatives, [37] or formation of isocyanate intermediates through Curtius rearrangement of acyl azides. Different possible routes are amidation cross-coupling reactions, [28][29][30][31][32] Beckmann rearrangement of ketoximes, [33][34][35][36] formation of azido intermediates convertible into amide derivatives, [37] or formation of isocyanate intermediates through Curtius rearrangement of acyl azides.…”

“…Thus, in this paper we describe our synthetic efforts involving the daunting task of preparing 2,5-disubstituted five-membered heterocycles with amide functionalities. Different possible routes are amidation cross-coupling reactions, [28][29][30][31][32] Beckmann rearrangement of ketoximes, [33][34][35][36] formation of azido intermediates convertible into amide derivatives, [37] or formation of isocyanate intermediates through Curtius rearrangement of acyl azides. [38]…”

An Electrochemical Beckmann Rearrangement: Traditional Reaction via Modern Radical Mechanism

“…[7] These harsh conditions still limit the application of Beckmann rearrangement. In recent years, some improved approaches of Beckmann rearrangement have been reported, such as organic initiator promoted reaction, [8] metal complex [9] or boronic acid [10] catalyzed rearrangement, pre-activation of oximes by equal or excess equivalent stoichiometric reagents, [11] the rearrangement executed by visible-light-driven generation of Vilsmeier-Haack reagent, [12] and the use of vapor phase [13] or supercritical water. [14] Although these strategies are efficient, most of them require additional chemical reagents or special equipments.…”

Mild, calcium catalysed Beckmann rearrangements

“…3 Other catalytic variants have been reported such as the use of TPAC, 4 gold, 5 chloral, 6 mercury 7 and iodine. 8 Recently Mhaske and co-workers reported a facile radical Beckmann rearrangement, 9 while Yadav and colleagues harnessed visible light to power the reaction. 10 Although all these methodologies provide the amides in good yields, they suffer from intolerance to various functional groups.…”

“…Subjecting erythromycin oxime (7) to the established conditions afforded the desired trapped intermediate (Scheme 3). Azithromycin (9) was then produced via the established reduction (8) and Eschweiler-Clarke methylation protocol. 18 Finally we turned our attention onto whether the reaction could be performed as a one pot procedure.…”