Flash Thermal Racemization of Chiral Amine in Continuous Flow: An Exploration of Reaction Space Using DoE and Multivariate Transient Flow

The robustness of the flash thermal racemization of optically active 1-phenylethylamine over Pd/γ-Al2O3 was studied by applying split-plot design-of-experiments (DoE), where the effects of temperature, flow rate, and concentration (3-factors) on the e.e. and selectivity (2-responses) were examined and quantified. The same effects were also interrogated using multivariate ramps in transient flow to produce response surfaces for the reaction space. The same set of optimal conditions for the process was identified by both approaches, and the same relationships between the variables were observed: while the extent of racemization (e.e.) can be directly correlated to temperature, a more complex relationship between temperature and flow rate on the selectivity was uncovered.