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

• Published in: The Journal of supercritical fluids 2023-08, Vol.199, p.105957, Article 105957
• Main Authors: Guo, Wei, Li, Ben, Chi, Haijun, Jiang, Zhongliang, Wei, Liu Qing, Ramsey, Edward D.
• Format: Article
• Language: English
• Subjects: Continuous flow chemistry in SF-CO2; Flow selection interfaces; Linked organic reactions; On-line SFC-UV/Vis-MS; Process analytical technology
• ISSN: 0896-8446; 1872-8162
• DOI: 10.1016/j.supflu.2023.105957

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-CO2). Each interface is designed to obtain on-line samples at different reaction progress points. Three single stage electrophilic annulation reactions performed in SF-CO2 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-CO2 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. [Display omitted] •Use of on-line SFC-DAD-MS system as a process analytical technology tool.•Organic syntheses in continuous flow supercritical carbon dioxide.•Synthesis of N-heterocyclics and Knoevenagel reaction, N-C and C-C bond formation.•Reaction monitoring at different progress points in linked continuous flow reactors.•Early stage detection of by-product reactions and characterization of impurities.