Accessing Novel Process Windows in a High-Temperature/Pressure Capillary Flow Reactor

High-temperature/pressure organic synthesis can be performed under continuous flow conditions in a stainless steel microtubular flow reactor capable of achieving temperatures of 350 degrees C and 200 bar (X-Cube Flash (TM)). Using these extreme experimental environments, the Claisen rearrangement of allyl phenyl ether together with the ensuing rearrangement chemistry of the resulting 2-allylphenol product was investigated. Reaction optimization was performed by changing the temperatures, pressures and flow rates on-the-fly. In addition, the high-temperature/pressure flow system allowed the study of these transformations in low boiling point solvents in or near their supercritical state. In general, the chemistry optimized under high-temperature microwave batch conditions could be successfully translated to a scalable flow regime.