Model system for the template effect of alkali and alkaline-earth metal ions on the formation of benzo-18-crown-6 in MeOH solution

Alkali and alkaline-earth metal ions exert a remarkable catalytic effect (template effect) on the cyclization of o-hydroxyphenyl 3,6,9,12-tetraoxa-14-bromotetradecyl ether (ArOH) to benzo-18-crown-6 (B18C6) in MeOH solution. This phenomenon is interpreted as resulting from two opposing factors, a rate-enhancing factor due to an increased proximity of chain ends in the cation-associated precursor ArO- and a rate-retarding factor due to interaction of the nucleophilic end of ArO- with the metal ion. Combination of previous equilibrium data with kinetic measurements from the present work provides a complete set of equilibrium constants for association of the seven cations Na+, K+, Rb+, and Cs+ and Ca2+, Sr2+, and Ba2+ with the four ligands ArOH, ArO-, B18C6, and T‡, the latter being the transition state for cyclization. Following our earlier suggestion, according to which the proximity effect is viewed as a sort of macrocyclic effect, i.e., the one in which the cyclic ligand is T‡ and the acylic ligand is ArO-, we now present an extrathermodynamic treatment indicating that the magnitude of the above macrocyclic effect is well represented by the KB18C6/KArOH ratio. This ratio provides an estimate for the upper limit of the template effect. The actually observed values are lower by a factor of ca. 4 because of reduction of nucleophilicity due to cation association. © 1983 American Chemical Society.