Premium
Toward a Continuous‐Flow Synthesis of Boscalid ®
Author(s) -
Glasnov Toma N.,
Kappe C. Oliver
Publication year - 2010
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201000646
Subject(s) - chemistry , palladium , flow chemistry , yield (engineering) , catalysis , triphenylphosphine , nitrobenzene , nitrile , homogeneous catalysis , solvent , organic chemistry , combinatorial chemistry , materials science , metallurgy
A two‐step continuous‐flow protocol for the synthesis of 2‐amino‐4′‐chlorobiphenyl, a key intermediate for the industrial preparation of the fungicide Boscalid ® is described. Initial tetrakis(triphenylphosphine)palladium‐catalyzed high‐temperature Suzuki–Miyaura cross‐coupling of 1‐chloro‐2‐nitrobenzene with 4‐chlorophenylboronic acid in a microtubular flow reactor at 160 °C using the tert ‐butanol/water/potassium tert ‐butoxide solvent/base system provides 4′‐chloro‐2‐nitrobiphenyl in high yield. After in‐line scavenging of palladium metal with the aid of a thiourea‐based resin, subsequent heterogeneous catalytic hydrogenation is performed over platinum‐on‐charcoal in a dedicated continuous‐flow hydrogenation device. The overall two‐step homogeneous/heterogeneous catalytic process can be performed in a single operation providing the desired 2‐amino‐4′‐chlorobiphenyl in good overall yield and high selectivity.