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

Publication date: 15 August 2018Source: Computational and Theoretical Chemistry, Volume 1138Author(s): Isac C. Nogueira, Josefredo R. PliegoAbstractAlkylation 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.Graphical abstract

Source: Computational and Theoretical Chemistry - July 6, 2018 Category: Chemistry Source Type: research