It is difficult to predict the future of flow chemistry, but the developments mainly in the last decade indicate that much of the huge potential of this enabling technology remains to be discovered. Flow chemistry has now found its way into research and development, not only in academic institutions but also in industry. This special issue of ChemSusChem is dedicated to flow chemistry. The various contributions range from two Reviews over several Communications to a series of Full Papers. They show the large breadth of applications to which flow chemistry is the key technology.
One Review by Hessel et al. looks at recent patents in microprocess technology, and certainly gives a good idea of which developments are currently under consideration. The other Review (Reiser et al.) highlights the use of metal-based reagents in microreactors. This is a research area of high interest, as other contributions in this special issue report on recent developments in this area. Uozumi et al. investigate the use of a polymeric palladium nanoparticle membrane for dehydrohalogenations using aqueous sodium formate as stoichiometric reducing agent. The generation and use of aryllithiums as reagents at ambient temperature in microreactors is demonstrated by Yoshida et al. in the synthesis of diarylethenes as interesting photochromic compounds. Gallium triflate on a solid support is used by Wiles et al. as an efficient catalyst for the Strecker reaction. The α-aminonitrile products could be obtained in higher yields than with homogeneous catalysis.
Other non-metal solid-supported catalysts are also being investigated: solid-supported peptides are used by Fülöp et al. in the addition of aldehydes to nitroolefines, leading to products with high enantiosleectivity. Pericàs et al. investigate polystyrene-bound proline residues as efficient catalysts for continuous-flow enantioselective aldol reactions. Environmental issues and cost-effectiveness play leading roles in the development of a continuous-flow process for the epoxidation of soybean oil, as shown by Kralisch et al. The suppression of side reactions is achieved by performing acid-catalyzed [2+2] cycloaddition reactions in a flow reactor. Takasu et al. report the synthesis of a series of cyclobutane derivatives using this methodology.
Safety issues are important in research and development, but even more in production processes. Dangerous reagents can be safely used in microreactors, as Sandford et al. show by the preparation and use of hypofluorous acid as one of the most powerful oxygen transfer agents. As this reagent is unstable, it has to be prepared directly before use but serves as a convenient reagent for the oxidation of various amines and azides in flow. We report the use of hot, concentrated sulfuric acid for Ritter reactions in a safe flow environment. Even the large-scale synthesis of amides is possible. Rutjes et al. use instable peracids for the dihydroxylation of alkenes in a continuous flow process and also demonstrate the possibility of an easy scale-up to preparative production volumes.
Novel methodology in continuous flow chemistry has already led to new processes and alternative reactions. Ley et al. are using gas-permeable tubing to introduce molecular oxygen into a reaction mixture. This is used to effect the copper-mediated Glaser–Hay coupling of alkynes to synthetically very useful 1,3-butadiynes. The organocatalyzed epoxidation of alkenes is performed efficiently by Bjørsvik et al. using a multi-jet oscillating disk reactor. The advantages of an electrochemical microreactor are shown by Brown et al. in the TEMPO-mediated electrocatalytic oxidation of alcohols to the corresponding carbonyl derivatives. The principles of coupling an ultrasound generator with microreactors is investigated thoroughly by Hübner and Jähnisch et al. A simple ester hydrolysis served as an example for the detailed analysis of this experimental setup.
All the contributions in this issue show the diverse state-of-the-art of flow methodology in chemistry and the potential it certainly holds for future developments. I am very thankful to all colleagues for their valuable contributions to this special issue on flow chemistry, and to the staff at ChemSusChem for their support and professional realization of this issue.