Waste-minimized access to diarylamines and triarylamines via Csp2–N coupling under batch and flow conditions

Abstract

In this study, we present a waste-minimized strategy for synthesising diarylamines and triarylamines via Buchwald–Hartwig coupling. These structural motifs rank among the top 20 most prevalent functional groups in biologically active molecules, and they are widely used in fields ranging from medicinal chemistry to materials science. The heterogeneous catalyst Pd/C was effectively employed under batch conditions and packed into the reactor for the flow setup. Our waste-reduction strategy utilises an azeotropic mixture of cyclopentyl methyl ether (CPME) derived from petrochemical waste and water. To enhance process circularity, the heterogeneous catalyst, phosphine-based ligand, and CPME were recovered and reused. The use of a biphasic CPME azeotrope as the reaction medium facilitated the process under flow conditions by enabling the solubilisation of all reaction components. Final product isolation was achieved thanks to an in-line liquid–liquid separator, which allowed for a significant reduction in waste generation.