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

Monitoring a synthesis reaction in real time 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 synthesis processes to be monitored, but most of the time it targets a specific reaction or compounds and involves solvents compatible with MS. In this study, a universal setup for the hyphenation of a microreactor with MS and based on two valves has been developed. This two-valve setup 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 setup evidenced a good repeatability and a linear response for the detection of the studied compounds. In addition, the dilution step included in the two-valve setup allows the 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%.

Automated summary

Monitoring synthesis reactions in real time is important for detecting intermediates, understanding reaction mechanisms, and identifying impurities. Spectroscopic methods may not be effective for complex mixtures, while mass spectrometry (MS) offers accuracy and sensitivity for detecting, quantifying, identifying, and characterizing reagents and species. This study developed a universal setup using two valves to hyphenate a microreactor with MS, which showed good repeatability and a linear response for analyzing molecules of different nature and hydrophilicity, even in non-MS-compatible solvents. The setup allowed for monitoring compounds synthesized at different concentrations and was successfully used in studying an amination reaction with high repeatability.