Toward a Continuous-Flow Synthesis of Boscalid®

✍ Scribed by Toma N. Glasnov; C. Oliver Kappe

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 238 KB
• Volume: 352
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.201000646

✦ Synopsis

Abstract

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.