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An integrated process including continuous-flow syntheses directly coupled to product isolation via continuous crystallization is presented. For the synthesis part, Ce0.495Sn0.495Pd0.01O2—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.

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Journal of Flow Chemistry
Authors: Lukas Hohmann, Safa Kutup Kurt, Sebastian Soboll and Norbert Kockmann

. 46. Ni , X.-W. Continuous Crystallisation and Manufacture; ACHEMA 2015, Frankfurt a.M., DE, 2015. uploads/2015/06/Achema-20 2015.pdf

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. Czyz , P. Valente , M. R. Hill , C. J. Doonan Chemical Communications 2015 , 51 , 14231 – 14234 “ Continuous crystallization of ZnO nanoparticles by spray flash evaporation versus batch synthesis ” M. Klaum ¨¹nzer L

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coworkers presented the utilization of centrifugal partition chromatography (CPC) for the continuous purification of multistep synthesis products as an alternative purification concept [ 52 ]. Continuous crystallization(s) have also been used in isolate, in

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