Effects of charge separation, effective concentration, and aggregate formation on the phase transfer catalyzed alkylation of phenol

The factors that influence the rate of alkylation of phenol under phase transfer catalysis (PTC) have been investigated in detail. Six linear, symmetrical tetraalkylammonium cations, Me ₄N ⁺, Et ₄N ⁺, (n-Pr) ₄N ⁺, (n-Bu) ₄N ⁺, (n-Hex) ₄N ⁺, and (n-Oct) ₄N ⁺, were examined to compare the effects of cationic radius and lipophilicity on the rate of alkylation. Tetraalkylammonium phenoxide·phenol salts were prepared, and their intrinsic reactivity was determined from initial alkylation rates with n-butyl bromide in homogeneous solution. The catalytic activity of the same tetraalkylammonium phenoxides was determined under PTC conditions (under an extraction mechanism) employing quaternary ammonium bromide catalysts. In homogeneous solution the range in reactivity was small (6.8-fold) for Me ₄N ⁺ to (n-Oct) ₄N ⁺. In contrast, under PTC conditions a larger range in reactivity was observed (663-fold). The effective concentration of the tetraalkylammonium phenoxides in the organic phase was identified as the primary factor influencing catalyst activity. Additionally, titration of active phenoxide in the organic phase confirmed the presence of both phenol and potassium phenoxide aggregates with (n-Bu) ₄N ⁺, (n-Hex) ₄N ⁺, and (n-Oct) ₄N ⁺, each with a unique aggregate stoichiometry. The aggregate stoichiometry did not affect the PTC initial alkylation rates.