A single-step synthesis of 1,3,4,6-tetraaryl-5-aryliminopiperazin-2-one

Chemical diversity is a strong driver in drug discovery, and chemical reactions that produce multi-substituted heterocycles can result in significant chemical diversity. Here, we report a reaction that leads to highly substituted piperazinone derivatives in a single step. This was discovered accidently while reacting phenylglyoxal and anilines under Povarov conditions. We elucidated the structure of the compound formed when 2-(4-trifluoromethyphenyl)-2-oxoacetaldehyde was reacted with 4-methoxyaniline as (1,4-bis(4-hydroxyphenyl)-5-[(4-hydroxyphenyl)imino]-3,6-diphenylpiperazin-2-one) (5e). The structure was confirmed after extensive spectral analyses, including correlation spectroscopy, nuclear Overhauser effect spectroscopy, heteronuclear single quantum correlation spectroscopy, and heteronuclear multiple-bond correlation nuclear magnetic resonance spectroscopy, in addition to high-resolution mass spectrometry. This reaction is unprecedented and can potentially be exploited as a short route to highly diversified heterocycles.

Automated summary

The study describes a reaction that leads to highly substituted piperazinone derivatives in a single step, providing a new pathway for the preparation of diverse compounds. The structure and mechanism of the reaction were confirmed through extensive spectral analyses and mass spectrometry, and it has the potential to serve as a rapid route to diversified heterocycles.