title: Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.
abstract: In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Heejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Chemical Engineering, POSTECH, Pohang 790-784, Korea.
authors.forename: Kyoung-Ik
authors.initials: KI
authors.lastname: Min
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Chemical Engineering, Pukyong National University, Busan 608-739, Korea.
authors.forename: Do Jin
authors.initials: do J
authors.lastname: Im
authors.affiliation: Department of Chemical Engineering, POSTECH, Pohang 790-784, Korea. dpkim@postech.ac.kr yoshida@sbchem.kyoto-u.ac.jp.
authors.forename: Dong-Pyo
authors.initials: DP
authors.lastname: Kim
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan. dpkim@postech.ac.kr yoshida@sbchem.kyoto-u.ac.jp.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis*; D000871:Anthelmintics / Q000138:chemical synthesis*; D001549:Benzamides / Q000138:chemical synthesis*; D056656:Lab-On-A-Chip Devices; D044085:Microfluidics / Q000379:methods*
chemical_list: D000814:Aniline Compounds; D000871:Anthelmintics; D001549:Benzamides; C000608136:afesal