This experimental study by Hawkins et al. examines route scouting in heterogeneous solid–liquid reactions, focusing on how mixing and sampling affect reaction kinetics and selectivity. Using the N-methylation of 1-phenylpiperazine with methyl p-toluenesulfonate and solid K₂CO₃, reaction time profiles were compared across three reactor setups: a small-scale overhead-stirred multi-reactor system (ReactALL, 5–10 mL), a commercially available overhead-stirred reactor (50–100 mL), and a two-dram vial with magnetic stirring.

The results show that mixing strongly impacts conversion and selectivity: overhead-stirred reactors stalled at ~50% conversion, while magnetically stirred reaction progressed further. This difference is due to magnetic stirring grinding the solid, increasing its surface area. Time-resolved sampling also revealed formation of a bis-methylated byproduct at later stages, providing a sensitive probe of chemoselectivity. Additional experiments demonstrated that grinding the solid base reproduces the kinetic behavior observed with magnetic stirring, confirming the mechanistic role of particle size and solid–liquid contact. Overall, the study demonstrates the importance of controlled mixing and representative sampling for reliable kinetic analysis in heterogeneous reactions.