Development of an Inline Tube-in-Tube Solvent Exchanger for Continuous-Flow Swap from High- to Low-Boiling Solvent

Abstract

Solvent swap from high- to low-boiling solvents still presents a huge challenge in the development of multistep continuous-flow processing. Herein, a miniaturized inline tube-in-tube solvent exchanger combining intensified convective mass transfer with droplet evaporation is presented. The design involves intimate contact between droplet and gas phases in countercurrent mode within a mesofluidic tube. Its solvent removal performance was evaluated by using pure solvents and binary mixtures. The results revealed that the commonly used solvents with low to medium boiling points (Tb < 100 °C) can be completely evaporated at room temperature without the need of heating. Significantly, high-boiling solvents can be efficiently removed at temperatures much lower than their boiling points. Its capacity for the separation of binary mixtures was corroborated by removing dichloromethane from a 50:50 mol % dichloromethane–dimethylformamide mixture and acetic acid from a 50:50 mol % p-nitroacetophenone–acetic acid mixture. A computational fluid dynamics (CFD) model based on the phase field approach was developed to quantitatively describe the droplet evaporation process, providing indepth evaporation dynamics and furthering our understanding on the concomitant phase change phenomenon. The comparison with other types of evaporators highlights its superior evaporative performance. To enable fast design and optimization of this type of evaporators, a correlation model was proposed to calculate the evaporation rate with good prediction performance. The usefulness of this device was demonstrated by performing a two-step continuous-flow synthesis of 4-aminoacetophenone. The combined experimental and CFD studies demonstrate that this tube-in-tube device can serve as a convenient and efficient tool for continuous solvent exchange, particularly from high- to low-boiling solvents, in continuous-flow synthesis.