Non-Aqueous Continuous-Flow Electrophoresis (NACFE): Separation Complement for Continuous-Flow Organic Synthesis

Continuous-flow organic synthesis naturally requires continuous-flow separation of reaction components. The most common continuous-flow separation approach is liquid-liquid extraction based on differential distribution of molecules between organic and aqueous phases. This approach has limited selectivity; it can hardly separate different hydrophobic organic molecules from each other. Continuous-flow electrophoresis can facilitate much more selective separation in a single phase, but it is currently limited to aqueous electrolytes which are incompatible with many hydrophobic organic molecules. Further, water electrolysis in aqueous electrolytes results in generation of large volumes of gas making steady-state operation a major technical challenge. Here, we introduce non-aqueous continuous-flow electrophoresis (NACFE) in which the electrolyte is a solution of an organic salt in an aprotic organic solvent. We demonstrate that NACFE can maintain stable separation of multiple species during 10 hours. The non-aqueous nature of NACFE and its ability to support steady-state operation make it suitable for its incorporation into continuous-flow organic synthesis.