Expedited Development through Parallel Reaction Screening: Application to PTC-Mediated Knoevenagel Condensation

Parallel microreactor screening enabled rapid identification of effective conditions for PTC-mediated Knoevenagel condensation between aldehyde ( 1 ) and thiazalone ( 2 ), affording a dramatic reduction in cycle time when compared to traditional conditions. Interesting facets of the reaction mechanism were revealed from kinetic profiling, specifically the operation of an extractive PTC mechanism with a pH optimum for the Knoevenagel condensation, a p K a optimum for the elimination reaction and the requirement for crystallization of aldol tautomer ( 4 ) to drive the reaction to completion.