Development of setups for real-time analysis of the effluent of a microreactor by mass spectrometry

Abstract

Monitoring in real-time a synthesis reaction could allow not only the detection of the intermediates involved in the synthesis to better understand its mechanisms but also the impurities. Spectroscopic methods could be performed but are not so performant when analyzing complex mixtures and could require specific properties for the detection of the molecules of interest, the presence of a chromophore moiety for example. Mass spectrometry (MS) may overcome these limitations and is able to reach the accuracy and sensitivity required to efficiently detect, quantify, identify and characterize the reagents and species produced during the synthesis. This is why the hyphenation of a microreactor with MS has already allowed to monitor synthesis processes, but most of the time targeting a specific reaction or compounds and involving solvents compatible with MS. In this study, a universal set-up hyphenated a microreactor with MS and based on two valves has been developed. This two-valve set-up has proven itself for the analysis of molecules of different nature and hydrophilicity, soluble in a large number of solvents even in non-MS-compatible ones. The developed set-up evidenced a good repeatability and a linear response for the detection of the studied compounds. In addition, the dilution step included in the two-valves set-up allows MS monitoring of compounds initially synthesized at different concentrations. Finally, it was successfully used to study an amination reaction allowing the detection of the reaction products in 4 min with good repeatability as RSD values of MS signals were lower than 17%.