Flow chemistry today: practical approaches for optimisation and scale-up
A general methodology is presented as a practical approach to the design of a continuous flow process and its subsequent optimisation and up scaling. Three examples of such designs are shown. The continuous flow Swern-Moffatt oxidation shows that even for ultrafast reactions, the same methodology is still feasible, resulting in an 8.5 g/h synthesis rate. Also, the continuous flow synthesis of explosive azides shows that preparative-scale safety issues at a 1 g/h synthesis rate can be more adequately dealt with. Lastly, as an example of what process automation can accomplish, we present the novel application of an automated screening of a model reaction (the Fischer esterification) with on-line gas-chromatographic analysis. Using this set-up, we found optimal reaction conditions within a working day using minimal amounts of reagents and labour, resulting in the continuous production of the target ester at a 67 mL/h rate.
As continuous flow chemistry is now maturing into a well-established and accepted technology (1-5) it becomes useful for researchers to define a common set of tasks to systematically design continuous flow processes and identify the optimal reaction conditions to successfully synthesise the target molecules on a preparative laboratory or industrial scale.
In this article we present the methodology we developed over the years and which is now routinely employed in our research groups on a large variety of reactions. This methodology is highlighted by a selection of three chemical reactions which were successfully converted into continuous flow processes, thereby exemplifying some major advantages over the corresponding batch processes: (i) the ability to attain sub-second reaction times, (ii) increased safety when handling potentially dangerous compounds, and (iii) automated on-line chromatographic analysis of a microreactor’s effluent.
FLOW CHEMISTRY METHODOLOGY
Design of a continuous flow process
Batch processing of a chemical reaction is inherently non-linear. Whenever rea ...