Ethyl 2‐Cyano‐2‐(2‐nitrobenzenesulfonyloxyimino) Acetate (ortho‐NosylOXY)‐Mediated Double Beckmann Rearrangement of Ketoximes under Microwave Irradiation: A Mechanistic Perception

Abstract

A method for Beckmann rearrangement using ethyl 2‐cyano‐2‐(2‐nitrobenzenesulfonyloxyimino) acetate (o‐NosylOXY) under microwave irradiation is reported. Ketoximes (19 examples) are converted to the corresponding amides/lactams with 69–97% yields in ∼10 minutes without any Lewis acid or co‐catalyst. This is an example of halogen‐free organocatalytic Beckmann rearrangement. Nuclear magnetic resonance (NMR)‐ and high‐resolution mass spectrometry (HRMS)‐based detailed mechanistic investigation suggest that o‐NosylOXY acts as an initiator. Such initiators are reported before based on density functional theory (DFT) calculations. However, we report here the HRMS signatures of two transient intermediates, the nitrilium ion and the nitrilium ion's dimeric species. Rigorous NMR‐based investigation of the reaction mechanism is performed. Our results indicate that the reported Beckmann rearrangement proceeds via two consecutive rearrangements.

The stable “F–SO2+” donor provides a mild and efficient approach to nitriles and amides

“…Various catalysts have been devised in recent years to facilitate the heterolysis of nitrogen–oxygen bond in order to achieve this transformation, but there are still certain drawbacks. Such as o -NosylOXY, 20 required microwave irradiation and high temperature. In 2020, Xu reported that HCl·DMPU assisted conversion of aldehydes into nitriles while HCl–DMPU is a solution emitting fumes.…”

Ethyl‐2‐Cyano‐2‐(2‐Nitrophenylsulfonyloximino)Acetate (ortho‐NosylOXY) Mediated One‐Pot Racemization Free Synthesis of Ureas, Carbamates, and Thiocarbamates via Curtius Rearrangement

“…On the other hand, Ethyl‐2‐cyano‐2‐(2‐nitrophenylsulfonyloximino)acetate ( ortho ‐ NosylOXY, I , Scheme 1) is a versatile coupling reagent that can be used for the synthesis of amides and peptides in both solid and solution phases, [24a] amide and nitrile from ketoxime and aldoxime respectively, [24b–c] acetal/thioacetal from aldehydes, [24d] benzoxazole, benzothiazole, [24e] and alcohols [24f] from a carboxylic acid. Besides these, we have previously reported Lossen's rearrangement by two similar reagents [25] .…”

Contemporary Approaches for Amide Bond Formation

“…[227] Nonetheless, Mandal and his colleagues achieved an organocatalyzed Beckmann rearrangement without the involvement of inorganic materials. [228] They employed o-NosylOXY (depicted in Figure 51a) under microwave irradiation and straightforward reaction conditions. This method exhibited a broad substrate scope and yielded minimal waste except during purification.…”