Theoretical study of the mechanism and regioselectivity of the alkylation reaction of the phenoxide ion in polar protic and aprotic solvents

Abstract

Abstract Alkylation of the phenoxide ion in the solution phase can take place on the oxygen atom (O-alkylation) and the carbon atoms of the aromatic ring in the ortho- and para-positions (C-alkylation). The reaction outcome depends on the alkylating molecule and the solvent. This work presents a density functional theory calculation (X3LYP and M08-SO functionals) of the possible reaction pathways for alkylation of phenoxide ions with ethyl chloride in the following solvents: water, methanol, and dimethyl sulfoxide. The solvent effect was included through the SMD and PCM models. Our results pointed out that O-alkylation was much more favorable than C-alkylation in the gas phase. Solvent effect favors C-alkylation, although it was unable to change the reactivity preference of O-alkylation, even in aqueous solution. Alkylation on the meta-carbon atom corresponded to a second-order saddle point and was the most unfavorable pathway. The calculations indicated that only O-alkylation would be observed, with an activation free energy of 23.6 kcal mol−1 in dimethyl sulfoxide solution, in good agreement with the experimental barrier of 20.8 kcal mol−1.