photoredox flow reactor™ hck1006-01-022

Description :

Overcoming Photoredox Chemistry Scale-Up Challenges Scaling up photoredox chemistry is often hindered by the low penetration of light into the reaction mixture (only a few millimeters), making the use of large reaction vessels impractical. The surface area is crucial for reducing reaction time. By conducting the reaction in flow, the surface area is significantly increased, which decreases the reaction time and enables continuous mode operation for scale-up. To address this challenge, we designed a flow reactor compatible with the PhotoRedOx Box™. This flow reactor utilizes PFA tubing and has a volume of 2 ml. Comparing reactions conducted in flow with those in batch, we observed a significant decrease in reaction time. Photoredox Flow Reactor Validation Reaction 1 Time to 95% conversion: Flow 30 min, batch 24h Reaction Protocol: In a 4-ml vial equipped with a Teflon septum, NiCl2-dme (1.1 mg, 5 μmol, 5 mol %) and dtbbpy (1.3 mg, 5 μmol, 5 mol %) were weighed. 1 ml of dry MeOH was added, and the mixture was stirred on an orbital shaker until fully dissolved. The solution was then evaporated to dryness at room temperature. Subsequently, Ir(dF-CF3-ppy)2(dtbpy) (1.1 mg, 1 μmol, 1 mol %) and 4-bromoacetophenone (9.95 mg, 100 μmol, 1 equiv.) were added. Next, 1 ml of dry acetonitrile was added, followed by Et3N (21 μl, 300 μmol, 3 equiv.) and aniline (4.65 mg, 100 μmol, 1 equiv.). The solution was sparged with nitrogen via a submerged needle for 5 minutes. Several batches of 100 μl of the solution were successively injected into the flow reactor placed in the EvoluChem PhotoRedOx Box with a blue Kessil LED using an injection module (Gilson). The samples were circulated using an HPLC pump at different flow rates to allow residence times of 5, 10, 15, 20, and 30 minutes. Reaction completion was monitored by LC-MS, using the ratio of bromoacetophenone to product. Flow Reactor Validation Reaction 2 Time to 95% conversion: Flow 30 min, batch 8h Reaction Protocol: In a 4-ml vial equipped with a Teflon septum, NiCl2-dme (1.1 mg, 5 μmol, 0.1 mol %) and dtbbpy (1.3 mg, 5 μmol, 0.1 mol %) were weighed. 1 ml of dry MeOH was added, and the vial was stirred on an orbital shaker until completely dissolved. The solution was then evaporated to dryness at room temperature. Subsequently, Ir(dF-CF3-ppy)2(dtbpy) (1.1 mg, 1 μmol, 0.1 mol %) and 4-bromoacetophenone (4.98 mg, 50 μmol, 1 equiv.) were added. Next, 1 ml of dry acetonitrile was added, followed by 2,6-lutidine (17.5 μl, 150 μmol, 3 equiv.) and potassium benzyltrifluoroborate (9.90 mg, 50 μmol, 1 equiv.). The solution was sparged with nitrogen via a submerged needle for 5 minutes. Several batches of 100 μl of the solution were successively injected into the flow reactor placed in the EvoluChem PhotoRedOx Box™ with a blue Kessil LED using an injection module (Gilson). The samples were circulated using an HPLC pump to allow a residence time of 30 minutes. Reaction completion was monitored by LC-MS, using the ratio of bromoacetophenone to the product.