Use of Fluorine Kinetic Isotope Effects in the Study of Steric Effects in Nucleophilic Aromatic Substitution Reactions

Leaving group fluorine kinetic isotope effects (F KIEs) have been determined in order to probe the influence of steric effects on the mechanism of the nucleophilic aromatic substitution (S N Ar) reaction of 2,4-dinitrofluorobenzene (DNFB) with 2- and 4-methylaniline, respectively. The 18 F/ 19 F KIE using isotopically labeled substrate was determined to be 1.0005 ± 0.0030 for 4-methylaniline and 1.0119 ± 0.0037 for 2-methylaniline in DMSO at 30 °C. The large F KIE for 2-methylaniline suggests rate-limiting leaving group departure for this sterically more hindered nucleophile, whereas the insignificant F KIE for the less sterically hindered 4-methylaniline indicates rate-limiting addition of the nucleophile.