Continuous flow synthesis of meso-substituted porphyrins with inline UV-Vis analysis

Abstract

Porphyrin derivatives have found diverse applications due to their attractive photophysical and catalytic properties, but remain challenging to synthesize, particularly at scale. Porphyrin synthesis thus stands to benefit from the more controlled environment, opportunities for efficient optimization, and potential for scale-up available in flow. Here, we have transferred Lindsey porphyrin synthesis into flow, enabling controlled timing for oxidation and neutralization steps and real time monitoring of the reaction mixture with inline UV-Vis analysis. For tetraphenyl porphyrin (TPP), inline UV-Vis showed the presence of protonated TPP, formed due to residual acid catalyst. Thus, inline monitoring allowed optimization of the neutralization step to improve yield. Three further porphyrin substrates were produced in flow; in two cases, the yield from inline UV was significantly higher than the yield from post-purification, identifying further yield losses that could be recovered by modifying the purification step. The workflow presented here can be adapted to multiple substrates to systematically optimise porphyrin yield, reducing the time needed to develop scalable routes to these valuable compounds.