Continuous Suzuki-Miyaura Reactions with Novel Ce-Sn-Pd Oxides and Integrated Crystallization as Continuous Downstream Protocol

An integrated process including continuous-flow syntheses directly coupled to product isolation via continuous crystallization is presented. For the synthesis part, Ce 0.495 Sn 0.495 Pd 0.01 O 2-δ was used as heterogeneous catalyst in a custom-made packed-bed reactor (the so-called “Plug and Play” reactor) for continuous Suzuki-Miyaura crosscouplings of various para - and ortho -substituted bromoarenes with phenylboronic acid using environmentally friendly aqueous ethanolic mixtures as reaction solvents. The reactions were stable for up to 30 h without any detectable catalyst deactivation. The desired biaryl products were obtained in gram scale with good to excellent yields and high selectivity. For three methyl-, ketyl-, and nitrile-functionalized biphenyl products, isolation was done using water as antisolvent in an integrated crystallization process as continuous downstream protocol. The desired products could be isolated with high purity and with yields of up to 95% for the overall process.