Monitoring Process-Scale Reactions Using API Mass Spectrometry

We present results using an unmodified nebulized assisted electrospray ionization (ESI) interface to observe a process-scale organic reaction (26 wt % in reactants) in real time. The approach offers distinct advantages over optical methods because unambiguous MW information can be obtained. The approach uses a series of pumps, which, after sampling the reactor, (1) quench the reaction, (2) reduce the concentration (3000×), and (3) add a proton-donating buffer for ionization. The approach is demonstrated with a piperidine-catalyzed Knoevenagel condensation reaction in toluene with informative results. The particular softness of ESI affords the formation of protonated parent ions almost exclusively. Reactions are tracked following [M + H] + ion signatures as a function of time. In addition to providing information about kinetic rates, mechanistic information was obtained via the observation of the Mannich base intermediate of the reaction. Use of the data in regard to absolute ion intensities as well as future applications are discussed.