Microreactor technology and continuous flow processing in general are key features in making organic synthesis both more economical and environmentally friendly. When preformed under a high-temperature/pressure process intensification regime many transformations originally not considered suitable for flow synthesis owing to long reaction times can be converted into high-speed flow chemistry protocols that can operate at production-scale quantities. This Focus Review summarizes the state of the art in high-temperature/pressure microreactor technology and provides a survey of successful applications of this technique from the recent synthetic organic chemistry literature.

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)

The energy consumed for four different organic transformations carried out under microwave and conventional heating under otherwise identical reaction conditions was measured with the aid of a Wattmeter. In the case of open-vessel reflux processing, microwave dielectric heating required significantly more energy than conventional techniques using oil baths or heating mantles. This is a consequence of the comparably low energy efficiency of the magnetron in converting electrical to microwave energy. Significant savings in energy were experienced by taking advantage of sealed-vessel microwave processing at high temperatures. When comparing a conventionally heated reflux experiment with a microwave-heated experiment using a superheated solvent in a sealed vessel, reaction times were reduced significantly from hours to minutes. The energy savings in these instances are, however, largely connected to the reduced reaction time and are not an inherent feature of microwave heating.

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°C and 200 bar (X-Cube Flash™). 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.

The use of passive heating elements made out of chemically inert sintered silicon carbide (SiC) allows microwave transparent or poorly absorbing reaction mixtures to be heated under microwave conditions. The cylindrical heating inserts efficiently absorb microwave energy and subsequently transfer the generated thermal energy via conduction phenomena to the reaction mixture. In the case of low to medium microwave absorbing reaction mixtures, the addition of SiC heating elements results in significant reductions (30-70%) in the required microwave power as compared to experiments performed without heating element at the same temperature. The method has been used to probe the influence of microwave power (electromagnetic field strength) on chemical reactions. Six diverse types of chemical transformations were performed in the presence or absence of a SiC heating element at the same reaction temperature but at different microwave power levels. In all six cases, the measured conversions/yields were similar regardless of whether a heating element was used or not. The applied microwave power had no influence on the reaction rate, and only the attained temperature governed the outcome of a specific chemical process under microwave conditions.