Automated Multi-Trajectory Optimization

In another example of application of the simplex method, McMullen et cd. [38] demonstrated the rapid optimization and scaling of a Heck reaction using an automated microreactor system with HPLC monitoring and feedback control. Optimal reaction conditions in the microreactor were determined after 19 automated experiments and required a relatively small amount of starting material. The reaction was then successfully scaled up 50-fold from a microreactor to a Coming meso-scale glass reactor using the optimal conditions determined by the microreactor system. 

In more complex reaction schemes, the terrain of the objective function will not point so directly to the optimal conditions. Thus, an expanded multi-trajectory optimization system is designed, allowing for the optimization of such a complex reaction system. This analysis takes into account the changing behavior of the objective function by re-analyzing the objective terrain and changing the search direction during the optimization [39,40]. 

This method focused on the overall approach used to conduct reaction optimizations, regardless of the reaction or the actual objective function. Thus, it would be possible to interchange objectives or even reactions using the same methodology. A well-knovm method that is often used to accomplish this is DoE, but this approach assumes that the objective function can be well modeled over its entirety by a low-order function. Here, no such assumption is necessary, and this approach is intended to be extendable to more complex systems where design of experiments would fail to adequately capture the nature of the objective function. 

The IR micro flow cell enables monitoring of the reaction s approach to steady state, ensuring that steady-state data are used for analysis. Thus, the next set of reaction conditions can begin as soon as the previous steady state had been reached and assessed, rather than waiting a fixed number of residence times and assuming that steady state has occurred, as done previously [35,38]. Moreover, this analysis can be performed directly in-line at reaction concentrations by using the entire reactor 

Method Number of trajectories Number of setpoints Total volume (ml) T (°C) r (min) Optimum X X/T Jpenahy 

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