REGIOSELECTIVITY IN THE REACTION OF AMBIDENT PHENOXIDE ION AND METHOXIDE AND HYDROXIDE IONS WITH 2,4,6-TRINITROANISOLE - KINETIC AND THERMODYNAMIC CONTROL

2,4,6-Trinitroanisole (TNA, 1), as the archetypal electron-deficient aromatic that possesses a leaving group, reacts with alkoxide ions, including methoxide, in media that contain appreciable amounts of dipolar aprotic solvents to yield a 1,3 anionic sigma-adduct as the product of kinetic control; the 1,3 adduct gives way over time to the thermodynamically more stable 1,1 adduct. This behavior, in which an initial 1,3 adduct isomerizes to a 1,1 adduct, is now classified as TC-1,1 (thermodynamic control favoring the 1,1 adduct) and has generally been taken to be ubiquitous. The present studios challenge this view. The salient features of the reaction of TNA with the ambident (O- and C-) nucleophile phenoxide, as studied by 400-MHz NMR spectroscopy, include initial formation of a 1,1 O-adduct, which only gives way at long times to a 1,3 para-bonded C-adduct of phenoxide. TNA is also intercepted by methoxide and hydroxide ions formed in situ through solvolytic pathways, which adhere to the TC-1,1 behavior. No 1,3 O-adduct of phenoxide is formed either prior to the 1,1 species or later in the reaction sequence. This fact is emphasized by low-temperature (-40-degrees-C) NMR studies made possible by the introduction of the novel CD3CN-glyme-d10 solvent system, where the 1,1 adduct is the only species observed (3 min after initiation of reaction). These observations are in accord with a system that obeys KC-1,1 regioselectivity (kinetic control favoring the 1,1 adduct), in which the 1,1 phenoxide O-adduct is both kinetically and thermodynamically favored. Four limiting TC and KC cases are considered, and the factors that favor one pattern of regioselectivity as compared to another are discussed with regard to the following: F-strain associated with approach of the nucleophile to C-1; stabilization afforded adducts by charge-separated canonical forms; stabilization of a later transition state for PhO- attack at C-1, due to relief of strain in that transition state; ion pairing; geminal electronegative disubstitution; and, in particular, steric and stereoelectronic effects in antiperiplanar rotameric forms of the 1,1 O-adducts.