Nitration Under Continuous Flow Conditions: Convenient Synthesis of 2‑Isopropoxy-5-nitrobenzaldehyde, an Important Building Block in the Preparation of Nitro-Substituted Hoveyda–Grubbs Metathesis Catalyst

Abstract

Herein, we describe the use of continuous flow chemistry for selective, efficient and reproducible nitration of 2-isopropoxybenzaldehyde to produce the desired 2-isopropoxy-5-nitrobenzaldehyde, an important building block in the preparation of a ligand of nitro-substituted Hoveyda–Grubbs metathesis catalyst. Nitration was done with red fuming HNO₃, and this challenging and hazardous process was performed using a flow-through silicon-glass microreactor equipped with a set of temperature sensors, and with a productivity of 13 g/h, providing us with a reproducible chemical process amenable for production of sufficient quantities of 2-isopropoxy-5-nitrobenzaldehyde for ongoing large-scale synthesis of nitro-substituted Hoveyda–Grubbs metathesis catalyst