Shaking Up the Friedländer Reaction: Rapid, Scalable Mechanochemical Synthesis of Polyaryl‐Substituted Quinolines

Abstract

Quinolines are a ubiquitous heterocyclic aromatic scaffold, which can be found in many natural and synthetic products. They are highly valued for their pharmacological and electrochemical properties, encouraging the discovery of new routes for quinoline synthesis and diversification. Polyaryl‐substituted quinolines have recently surged as useful substrates for a wide variety of applications, yet their synthetic routes remain difficult and inefficient. Herein, we report a rapid and novel mechanochemical Friedländer synthesis of polyaryl‐substituted quinolines under basic conditions using ball milling. Optimized reaction conditions result in moderate to excellent yields ranging from 69% to >95% and demonstrates broad functional group tolerance at 1 hour reaction times. We further demonstrate a new route for the synthesis of photocatalyst DPQN2,4‐di‐OMe and photo‐ligand PPQN2,4‐di‐OMe as well as OLED donor‐acceptor pCzPPQ, electron transport material oligoquinoline TQB and organic semiconductor DPA. A gram‐scale reaction was also achieved using Resonant Acoustic Mixing (RAM), providing an isolated yield of 87% after a simple recrystallization in ethanol.