Ring Opening/Site Selective Cleavage in N-Acyl Glutarimide to Synthesize Primary Amides

Abstract

A LiOH-promoted hydrolysis selective C−N cleavage of twisted N-acyl glutarimide for the synthesis of primary amides under mild conditions has been developed. The reaction is triggered by a ring opening of glutarimide followed by C−N cleavage to afford primary amides using 2 equiv of LiOH as the base at room temperature. The efficacy of the reactions was considered and administrated for various aryl and alkyl substituents in good yield with high selectivity. Moreover, gram-scale synthesis of primary amides using a continuous flow method was achieved. It is noted that our new methodology can apply under both batch and flow conditions for synthetic and industrial applications.

B2(OH)4-Mediated Reductive Transamidation of N-Acyl Benzotriazoles with Nitro Compounds En Route to Aqueous Amide Synthesis

“…The main obstacle originates from the strong resonance stabilization effect in amides, which makes most amide C–N bonds too stubborn to be cleaved . In this wise, Lewis acid additives (Al, Sc, Ti, Zr, Fe, and others) or transition metal catalysts , or transition-metal-free protocols have been introduced to trigger the transamidation of amides, especially the tertiary ones (Scheme a). However, the reactions either proceed with incomplete conversion or require very high temperatures or specifically activated substrates .…”

Stabilizing the C−N Double Bond Character in Fumaramide with the Aid of Superacids

“…The NBO analysis of the neutral compound confirmed that the nitrogen, as well as the carbon atom of the amide moiety, are sp 2 -hybridized. The nitrogen atom possesses one lone pair, occupied with 1.74 e À , which is available for contributing to planar amidic bond resonance (n N !π* C=O conjugation), [5,23] which is illustrated in Figure 7. According to the NBO calculations, the oxygen atom reveals sp-hybridization.…”

The copper-catalyzed oxidative radical process of site selective C–N bond cleavage in twisted amides: batch and continuous-flow chemistry

“…45 Recognizing that selective C–N bond cleavage in activated amide is a necessary process, 46,47 we established the synthesis of primary amide via hydrolysis in base or acid medium. 48,49 Yet, the highly reactive sensitive functional groups (esters or nitriles) undergo hydrolysis eventually which corresponds to substantial difficulties in chemoselectivity under basic or acidic medium which is considered to be a contemporary challenge. Practical and new catalytic methods for synthesizing primary amides in a simple, efficient, and eco-friendly manner are in major demand in pharmaceuticals.…”