Inversion of kinetic and thermodynamic preferences in Meisenheimer complex formation: regioselectivity in the reaction of 2,4,6-trimethylphenoxide ion with 2,4,6-trinitroanisole and the importance of stereoelectronic factors

Abstract

To probe regioselectivity in Meisenheimer complexation, the reaction of 2,4,6-trimethylphenoxide ion (MesO - ) with 2,4,6-trinitroanisole (TNA) was followed by 1 H and 13 C NMR spectroscopy in the new low-temperature solvent acetonitrile-glyme (1:1, v/v) at -40 o C to ambient temperatures. The key results include finding a kinetic preference for C-1 attachment and that the σ-adduct that results from C-3 attack is thermodynamically more stable (K1T3 behavior); this behavior is in direct contrast to the «normal» C-3 to C-1 isomerization pathway displayed by alkoxides and hydroxide with TNA (K3T1 behavior) as well as different from the regioselectivity shown by the phenoxide ion as an O-nucleophile (K1T1 behavior)