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

Abstract

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.