Flow chemistry today: practical approaches for optimisation and scale-up
A general methodology is presented as a practicalapproach to the design of a continuous flow process and itssubsequent optimisation and up scaling. Three examples ofsuch designs are shown. The continuous flow Swern-Moffattoxidation shows that even for ultrafast reactions, the samemethodology is still feasible, resulting in an 8.5 g/h synthesisrate. Also, the continuous flow synthesis of explosive azidesshows that preparative-scale safety issues at a 1 g/hsynthesis rate can be more adequately dealt with. Lastly, asan example of what process automation can accomplish,we present the novel application of an automated screeningof a model reaction (the Fischer esterification) with on-linegas-chromatographic analysis. Using this set-up, we foundoptimal reaction conditions within a working day usingminimal amounts of reagents and labour, resulting in thecontinuous production of the target ester at a 67 mL/h rate.