On-line SFC-UV/Vis-MS using flow selection interfaces to monitor continuous flow single and sequential stage organic reactions in supercritical carbon dioxide

Two flow selection interfaces have been developed for connecting single or linked reactors with on-line SFC equipped with UV/Vis diode-array (DAD) and mass spectrometer detectors coupled in series (SFC-DAD-MS). This process analytical technology system, enabled the study of reactions performed in supercritical fluid carbon dioxide (SF-CO 2 ). Each interface is designed to obtain on-line samples at different reaction progress points. Three single stage electrophilic annulation reactions performed in SF-CO 2 using aniline, indole and pyrrole as amine reactants to synthesize N-heterocyclic products within a stirred continuous flow reaction vessel containing montmorillonite K-10 catalyst were monitored. Also, both stages of a two step synthetic procedure conducted within two connected continuous flow reaction coil systems were monitored using on-line SFC-DAD-MS. The first step involved a Knoevenagel reaction in SF-CO 2 that provided a continuous feed to perform a second stage acetylation reaction. Use of on-line SFC-DAD-MS enabled early detection and characterization of unexpected by-products.