Unexpected Intramolecular Phosphite‐Mediated Amide Coupling To Yield 3,5‐Dioxo‐1‐Piperazines
Year: 2021
Type: article
Abstract: The synthesis of tripodal carboxamide ligands using one‐pot phosphite coupling reactions with nitrilotriacetic acid (NTA) and 4‐substituted anilines is well established. Generation of such tripodal ligands using ortho ‐substituted anilines ( 2,6−R ArNH 2 , R=F, Me, i Pr) has proven to be challenging. The reaction between NTA and 2,6−R ArNH 2 using triphenylphosphite as a coupling reagent did not yield the desired tripodal carboxamide. Rather, the formation of 3,5‐dioxo‐1‐piperazine intramolecular coupling products N‐(2,6‐difluorophenyl)‐3,5‐dioxo‐1‐piperazine‐N‐(2,6‐difluorophenyl)acetamide ( 1 ), N‐(2,6‐dimethyphenyl)‐3,5‐dioxo‐1‐piperazine‐N‐(2,6‐dimethylphenyl)acetamide ( 2 ) and N‐(2,6‐diisopropylphenyl)‐3,5‐dioxo‐1‐piperazine‐N‐(2,6‐diisopropylphenyl)acetamide ( 3 ) was observed. All three compounds have been extensively characterized using nuclear magnetic resonance, Fourier‐transform infra‐red and mass spectrometry. X‐ray diffraction analysis yielded solid state structures of 2 and 3 . Substituents at the ortho position of aniline thus favours intramolecular cyclization over the formation of tripodal carboxamide ligands, preventing preparation of the desired bulky ligand.
Source: ChemistrySelect
Authors: Philipp Heim, Brendan Twamley, John O'Brien, Aidan R. McDonald
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Awards: G137528073, G2290212825
OpenAlex ID: W3203837618