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

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.

Automated summary

A LiOH-promoted hydrolysis selective C-N cleavage method for the synthesis of primary amides under mild conditions has been developed. The reaction shows high selectivity and yield for various aryl and alkyl substituents, and can be applied for gram-scale synthesis using a continuous flow method. This new methodology is applicable for both batch and flow conditions in synthetic and industrial applications.