Continuous flow reactor for the hydrogenation of organic substrates using novel catalytic static mixers.

Rapid acquisition of kinetic data is demonstrated with a commercial meso-scale flow reactor, using a step-change in flow rate or 'push-out' from the flow line. For thermolysis of 1,3-dioxin-4-ones (1), we obtain excellent reproducibility in the activation energies measured from spectroscopic data collected by in-line UV or transmission FT-IR monitoring of the output during the transitional period between two flow rates (± 3 kJ mol -1 , 0.7 kcal mol -1 ). Analysis of multi-component UV and IR data is conducted using an orthogonal projection approach (multivariate curve resolution by alternating least squares) for complex spectra, or by calibration-less integration of non-overlapping peak absorbance. All analysis methods were validated using off-line 1 H NMR analysis, and kinetic parameters obtained using the method of a flow rate step-change were validated against conventional steady-state measurements in which time-series data were acquired across multiple experiments. Thermal transfer and dispersion effects are addressed. The experimental methods described herein are valuable for accelerated reaction study and in process development.

Ketenes were generated by the thermolysis of alkoxyalkynes under flow conditions, and then trapped with amines and alcohols to cleanly give amides and esters. For a 10 min reaction time, temperatures of 180, 160, and 140 °C were required for >95 % conversion of EtO, iPrO, and tBuO alkoxyalkynes, respectively. Variation of the temperature and flow rate with inline monitoring of the output by IR spectroscopy allowed the kinetic parameters for the conversion of 1-ethoxy-1-octyne to be easily estimated (Ea = 105.4 kJ/mol). Trapping of the in-situ-generated ketenes by alcohols to give esters required the addition of a tertiary amine catalyst to prevent competitive [2+2] addition of the ketene to the alkoxyalkyne precursor.

Ketenes are generated in situ by thermolysis of ethoxyalkynes under flow conditions and trapped with amines or alcohols to form amides and esters respectively.