Unexpected Inhibition of the Knoevenagel Condensation in Methanol by Iodonium Salt Served as Electrophilic Activator

Abstract

Halogen bond donors are recognized as electrophilic catalysts in reactions involving carbonyl compounds. This study describes an unexpected inhibition of the Knoevenagel condensation by the catalyst. To elucidate the intricacies of the inhibition mechanism, the overall reaction order and rate constants were determined using ¹H NMR spectroscopy, and further experiments with different nucleophiles were conducted. The findings revealed that the inhibition of the primary reaction is attributed to a substantial acceleration of the side reaction involving aldehyde methanolysis, which hinders the formation of the final alkene product.