Continuous-Flow Diazotization of Weakly Basic Aromatic Amines in a Microreaction System

Abstract

Due to the characteristics of high transfer efficiency, controllable process, and intrinsic safety in microreactors, there have been many studies on the miniaturization of diazotization reactions. However, diazotization of weakly basic aromatic amines is difficult to be reformed by continuous microreaction technology due to its poor solubility. In this paper, first, by improving the crystallization process, the miniaturization of diazotization with low solid content was realized. The effects of various parameters (flow rate, temperature, reagent dosage, and concentration) on the reaction yield were investigated systematically. As for high solid content, by introducing the gas–liquid Taylor flow and ultrasonic assistance, the mass transfer process was strengthened, and the slurry flow pattern was improved. Finally, at 0.40 mol/L, a residence time of 94 s in the delay loop with a 5 °C cold trap was employed to produce a diazonium salt in 96% yield with high stability.