Reactivity and molecular recognition: Amine methylation by an introverted ester

We report a host molecule with an inwardly directed methyl ester and its reaction with a series of tertiary amines. The reaction product is a complex of the host carboxylate with a guest quaternary ammonium salt. The rate of the reaction is highly dependent on the suitability of the amine to occupy the host cavity and the intrinsic reactivity of the resulting complex. A kinetic study of the reaction of 2-(dimethylamino)ethanol to produce choline gives the activation parameters ΔH‡ = 25.1 ± 0.5 kcal mol-1= and ΔS‡ = 12 ± 2 cal mol-1 K-1. The complex, once formed, is poised to reach the transition state; a rate acceleration of greater than 2 × 104 fold is estimated when compared with similar reactions having no supramolecular effects. Copyright © 2003 American Chemical Society.