Counting bubbles: precision process control of gas–liquid reactions in flow with an optical inline sensor

摘要: Quality by Design encouraged the US Food and Drug Administration (FDA) in continuous flow synthesis requires tight monitoring of all reaction input output parameters to improve reproducibility eliminate process rejects. Reaction monitoring, however, relies on costly (over 10 000$) analytical technology (PAT) – one factors that prevents wider utilisation processes. In this work, we show gas–liquid reactions can be monitored using low-cost (10$) hardware an optical liquid inline sensor allows instantaneous analysis gas fraction a moving stream. We discuss application for various reactions. Gas-consuming such as hydrogenation are easiest implement because without calibration provides accurate readings close complete consumption gas. Gas-evolving but require determine accurately. Operation was demonstrated self-optimised proportional–integral (PID) algorithm which adjusted substrate concentration provide high (but not full) pre-defined hydrogen consumption. The optimised agreed with product range substrates hydrogenated under pressures different selectivities. also proven efficient tool adapting conditions catalyst deactivation 2-methyl-3-butyn-2-ol semi-hydrogenation autonomous reactor allowed turn-over number (TON) 2.7 × 106 reached value 1.5 107 expected till twofold decrease activity. TON values significantly higher than those observed batch reactors (∼103) even case re-use (105) demonstrating substantial improvement sustainability operating control.