Interfacing supercritical fluid reaction apparatus with on-line liquid chromatography: Monitoring the progress of a synthetic organic reaction performed in supercritical fluid solution

• Supercritical fluid reaction apparatus interfaced with liquid chromatography.
• Development of a chromatography based process analytical technology procedure.
• Monitoring the progress of organic reactions in supercritical fluid solution.
• Rapid process optimization compared with use of off-line analytical procedures.
• Very rapid rate of an esterification reaction in supercritical fluid solution.

An interface has been developed that connects a supercritical fluid reaction (SFR) vessel directly on-line to a liquid chromatograph. The combined SFR-LC system has enabled the progress of the esterification reaction between phenol and benzoyl chloride to synthesize phenyl benzoate in supercritical fluid carbon dioxide solution to be dynamically monitored. This was achieved by the periodic SFR-LC analysis of samples directly withdrawn from the esterification reaction mixture. Using the series of SFR-LC analysis results obtained for individual esterification reactions, the reaction progress profile for each esterification reaction was obtained by expressing the measured yield of phenyl benzoate as a function of reaction time. With reaction temperature fixed at 75 °C, four sets (n = 3) of SFR-LC reaction progress profiles were obtained at four different SFR pressures ranging from 13.79 to 27.58 MPa. The maximum SFR yield obtained for phenyl benzoate using a standard set of reactant concentrations was 85.2% (R.S.D. 4.2%) when the reaction was performed at 13.79 MPa for 90 min. In comparison, a phenyl benzoate yield of less than 0.3% was obtained using the same standard reactant concentrations after 90 min reaction time at 75 °C using either: heptane, ethyl acetate or acetonitrile as conventional organic reaction solvents.