Continuous‐Flow Microreactor Chemistry under High‐Temperature/Pressure Conditions

Abstract

High‐temperature organic synthesis can be performed under continuous‐flow conditions in a stainless steel microtubular flow reactor capable of achieving temperatures of 350 °C and 200 bar. Under these extreme experimental environments transformations normally performed in a high‐boiling solvent at reflux temperature – or under sealed‐vessel microwave conditions – can be readily converted to a flow regime by using lower boiling solvents in or near their supercritical state.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Selected Examples of High‐Pressure Reactions in Glass Microreactors

“…The reaction rate increased by about one order of magnitude at ambient conditions compared to conditions at 51 bar and 71°C. A different type of continuous-flow microreactor has recently been introduced by the group of Kappe [17]. It concerns a stainless-steel microtubular flow reactor (4, 8, and 16 mL volume) capable of achieving temperatures of 350°C and pressures ranging from 50 to 200 bar using an HPLC pump.…”

Flow Chemistry of the Kolbe‐Schmitt Synthesis from Resorcinol: Process Intensification by Alternative Solvents, New Reagents and Advanced Reactor Engineering

“…Only by high-pressure operation at 200 bar can the product be formed, whereas at 10 bar no product formation was observed. Kappe et al [30] depicted the advantages of a directly, by electric resistance heated flow reactor made of stainless-steel coils for many examples. Processing of a cycloaddition conventionally done with high-boiling solvents under sealed-vessel batch microwave conditions could be transferred towards lower-boiling solvents when using significantly higher pressures.…”

Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

“…The most widely used are the Leimgruber-Batcho, [8], Reissert [9], and Fischer [10] indole syntheses. Some preparations of indoles using continuous-flow technology have also been recently reported in the literature, notably some Fisher indole syntheses by the groups of Watts [11] and Kappe [12]. A more recent preparation of indoles using flow chemistry was also described by Seeberger [13] and involved the thermolysis of azide and C-H insertion of nitrene [13].…”