Flow Markers in Microreactors: A Generally Applicable Chromatographic Method for Monitoring Flow Rates During Reactions

Abstract

Abstract:Microreactors have found widespread use for continuous flow synthesis and reaction optimization. Flow rates are critical factors with respect to the latter application because they are used to set screening parameters such as reaction time and stoichiometric ratios. However, the set flow values of pumps for nanoliter to microliter volume reactors are quite often not sufficiently accurate. In this paper we present a generally applicable chromatographic method to analyze flow rates during microreactor reaction screening. By adding flow markers to all reactant and reagent flows and performing conventional GC analysis on all samples, an accurate flow rate was calculated. The deviation between the set flow values and the measured flow rates was shown for a standard continuous flow experiment. The implications of this deviation for reaction optimization were demonstrated via a model Swern-Moffatt oxidation reaction, which showed that accurately measured flow rates are critical for correct data interpretation.

Continuous flow azide formation: Optimization and scale-up

“…The product sample obtained from the microreactor was collected in dichloromethane containing 2‰ cyclooctane as an external standard. Accurate flow rates were calculated using our recently developed flow marker methodology [27].…”