Counter-ion and solvent effects in the C- and O-alkylation of the phenoxide ion with allyl chloride

The alkylation reaction of the phenoxide ion with allyl chloride can take place in the oxygen atom or in the carbons of the aromatic ring in the ortho position. Experimental studies have suggested that solvent effects and ion pairing are important for the regioselectivity. In this work, this reaction has been studied by means of theoretical methods using density functional theory, continuum solvation models, and inclusion of some explicit water molecules. It was found that O-alkylation is the only product in the reaction of free phenoxide ion in the gas phase. Inclusion of the solvent effect induces an activation barrier, and although the effect is more important for O-alkylation, it is not enough to reverse the major O-alkylation reaction path. When the reaction via the ion pair was considered, it was found that attack in the C3 carbon of the allyl chloride in the syn orientation of the leaving chloride ion leads to a stable transition state, with close activation barriers for both O- and C-alkylations. Inclusion of the solvent effect to the ion pair reaction makes both the reaction barriers closer (difference of 0.2 kcal mol(-1)), in excellent agreement with the experimental data. The absolute theoretical free energy barriers also reproduce the experimental barriers with a deviation of 3.5 kcal mol(-1). Thus, theoretical calculations point out that both ion pairing and solvation are critical for controlling reactivity and regioselectivity of this reaction.