Periodic Reporting for period 1 - ElectronsOnRun (Electrochemical fluorination under microflow conditions)
Reporting period: 2022-09-01 to 2024-08-31
ElectronsOnRun adopts a continuous-flow electrochemical microreactor to generate trifluoromethylated products without supporting electrolytes or additives, using electricity as a clean reagent. Electrochemistry is ideal for sustainable synthesis, providing precise control over reaction conditions and reducing waste. When paired with flow technology, these advantages are maximized: the high surface-area-to-volume ratio in a microflow cell enhances yield and selectivity, while continuous processing supports safer, scalable production with reduced material and energy consumption.
This innovative approach aligns with the European Union’s sustainability objectives and the Green Deal’s commitment to greener chemical production. By advancing electrochemical flow technology, ElectronsOnRun not only addresses pressing industrial and environmental needs in pharmaceutical synthesis but also lays the groundwork for broader applications of green chemistry and safer, sustainable manufacturing.
Design and Optimization of the Microflow Electrochemical Cell: A custom electrochemical microflow reactor was designed to operate without supporting electrolytes or additives, eliminating the need for metals and simplifying product purification. Using the Langlois reagent as the source of trifluoromethyl radicals, we optimized reaction conditions—such as flow rate, current density, and electrode material—to maximize yield and selectivity.
Reaction Mechanism and Electrochemical Efficiency Studies: We conducted detailed electrochemical studies to understand the reaction pathway. Cyclic voltammetry was used to analyze oxidation potentials and validate the electrochemical generation of trifluoromethyl radicals. These studies confirmed that the flow system's unique high surface-area-to-volume ratio allowed precise control over the reaction, minimizing side reactions and electrode fouling.
Comparative Performance with Batch Systems: We benchmarked the microflow cell against batch systems under identical conditions, finding that the flow system achieved an 82% yield compared to just 22% in batch mode. This demonstrated the significant efficiency and sustainability benefits of the continuous-flow setup.
Extended Substrate Scope and Scalability: The optimized process was applied to a range of enamide substrates, yielding several trifluoromethylated derivatives with high efficiency. We established that the setup could be scaled for continuous production by integrating automated flushing to maintain electrode activity, making the process suitable for industrial applications.
Main Achievements:
Established an additive-free, scalable electrochemical process for trifluoromethylation in continuous flow, achieving yields up to 82%.
Demonstrated the advantages of flow electrochemistry over batch methods, particularly in yield and environmental impact.
Validated the process for various substrates, showing versatility and potential for broad application in pharmaceutical synthesis.
Potential Impacts
The outcomes of this project have significant implications for pharmaceutical and fine chemical industries:
Environmental and Economic Benefits: The electrochemical flow method reduces waste and energy consumption, aligning with global sustainability goals and EU Green Deal objectives. Its reduced reliance on hazardous reagents and minimal purification needs offer both environmental and economic advantages, particularly for industries transitioning to greener processes.
Scalability and Industrial Relevance: The demonstrated scalability and compatibility with continuous production make this process highly attractive for industrial uptake. The method's high yield, versatility across substrates, and reduced resource use provide a viable alternative to conventional batch processes, supporting the industry’s move toward efficient, high-throughput synthesis methods.
Innovation in Green Chemistry: This project sets a new standard for green chemistry applications in electrochemical synthesis. The additive-free, flow-based approach could serve as a model for developing other sustainable methods for pharmaceutical synthesis, establishing a framework that minimizes waste and improves overall process safety.