Towards an approach to small-scale aryllithium flash flow chemistry using low-cost, low internal volume reactors.

Two low-cost reactors for aryllithium generation and trapping with an electrophile in flow chemistry have been developed for use with small quantities of limiting reagent (≤ 600 μmol) using reductions in flow rates as the approach to miniaturisation. To this end, a number of inexpensive, commercially available mixing elements were characterised via model lithium-halogen exchange reactions to determine their performance at low (< 5 mL / min) flow rates. From these studies, a glass chip mixer, and 250 μm tee-pieces were identified as suitable for use at low flow rates and therefore incorporated into the aforementioned reactors. These reactors were demonstrated to be suitable for the successful lithiation and trapping of a selection of aryl bromide substrates.