Toward a Continuous-Flow Synthesis of Boscalid

• Published in: Advanced synthesis & catalysis Vol. 352; no. 17; pp. 3089 - 3097
• Main Authors: Glasnov, Toma N., Kappe, C. Oliver
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 22.11.2010; WILEY‐VCH Verlag
• Subjects: cross-coupling; flow chemistry; heterogeneous catalysis; homogeneous catalysis; hydrogenation; microwave chemistry
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201000646

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.