Crossing the threshold from accelerated substitution to elimination with a bifunctional macrocycle

Abstract

A previously reported macrocyclic amine with anion binding amide residues can be N-alkylated at highly accelerated reaction rates to give quaternary ammonium products. This present study examines the reactivity with 1,2-disubstituted ethanes. Accelerated substitution is observed with 1,2-dichloroethane (5000 times faster than analogous control amines); whereas, accelerated elimination is the outcome with 3-halopropionitriles (10 000 times faster than analogous control amines). The structure of the protonated form of the macrocycle is analyzed by X-ray diffraction. The rates of elimination for 3-chloro, 3-bromo and 3-iodopropionitrile were measured and the relative order of second-order rate constants with triethylamine was 1 : 43 : 182 which reflects the expected order of leaving group abilities. In the case of the macrocycle, the relative order of second-order rate constants was 1 : 29 : 61. The macrocyclic cavity preferentially stabilizes the charge developing on the smaller and more basic Cl⁻ leaving group. The kinetic data are consistent with a bimolecular syn elimination mechanism.