TEMPO-Promoted Mono- and Bisimidation of Tertiary Anilines: Synthesis of Symmetric and Unsymmetric N-Mannich Bases

A TEMPO-promoted method was developed for the synthesis of symmetric bis-N-Mannich bases via sequential activation of two alpha,alpha '-amino C(sp3)-H bonds of N,N-dimethylanilines under mild conditions. This methodology was further extended for monoimidation of alpha-amino-functionalized methylanilines to give unsymmetric N-Mannich bases in good to high yields. Several control experiments were performed, and the coupling reaction outcomes indicated that the oxoammonium (TEMPO+) species is involved in the reaction.

Automated summary

A TEMPO-promoted method for the synthesis of symmetric bis-N-Mannich bases via sequential activation of two alpha,alpha'-amino C(sp3)-H bonds of N,N-dimethylanilines under mild conditions is developed. This methodology is further extended for monoimidation of alpha-amino-functionalized methylanilines to give unsymmetric N-Mannich bases in good to high yields. Control experiments indicate the involvement of oxoammonium (TEMPO+) species in the coupling reaction outcomes.