Alkylation of Phenol:  A Mechanistic View

Abstract

The current work utilizes the ab initio density functional theory (DFT) to develop a molecular level of the mechanistic understanding on the phenol alkylation in the presence of a cation-exchange resin catalyst, Amberlyst-15. The catalyst is modeled with the benzene sulfonic acid, and the effect of this acid on olefins such as isopropene (i-Pr) and tributene (t-Bu) in a phenol solution mimics the experimental condition. A neutral-pathway mechanism is established to account for early-stage high concentration of the phenolic ether observed in experiments. The mechanism involves an exothermic reaction between olefin and the benzene sulfonic acid to form ester followed by three reaction pathways leading to direct O-alkylation, o-C-alkylation, and p-C-alkylation. Our calculations conclude that O-alkylation to form the phenolic ether is the most energetically favorable in the neutral condition. An ionic rearrangement mechanism describes intramolecular migrations of the alkyl group from the phenolic ether to form C-alkylphenols, while the positively charged protonation significantly lowers transition barriers for these migrations. The ionic rearrangement mechanism accounts for high yields of o-C-alkylphenol and p-C-alkylphenol. Competition between the H atom and the alkyl R group at the substitutive site of the protonated ortho configuration is found to be the determining factor to the ortho/para ratio of C-alkylation products.

Liquid phase alkylation of anisole and phenol catalyzed by niobium phosphate

“…The alkylation of m-cresol with t-butanol were evaluated and the authors suggested that the strong acidic sites present in the catalysts are responsible for the C-alkylation. 13 A systematical theoretical study using ab initio calculation 21 and ab initio density functional theory (DFT) 12 were reported in the literature. They concluded that O-alkylation to form the phenolic ether is the product most energetically favorable in neutral conditions and an ionic rearrangement mechanism describes intramolecular migrations of the alkyl group from the phenolic ether to form C-alkylphenols.The intermediate from the C-alkylation is more stable and as a result, the O-alkylated products disappear gradually.…”

“…They concluded that O-alkylation to form the phenolic ether is the product most energetically favorable in neutral conditions and an ionic rearrangement mechanism describes intramolecular migrations of the alkyl group from the phenolic ether to form C-alkylphenols.The intermediate from the C-alkylation is more stable and as a result, the O-alkylated products disappear gradually. 12,21 The liquid phase alkylation of phenol with 1-octen-3-ol over niobium phosphate an ionic rearrangement of the O-alkylated products to C-alkylated products can occur. A mechanistic study are in progress in our laboratory to clarify this point.…”

“…Alkylation of phenol has an additional complication because of the possibility of the alkyl attacking to the phenolic oxygen (O-alkylation) that leads to an ether formation beside desirable alkylations at the aromatic ring (C-alkylation). [11][12][13] Information about the use of niobium compounds for the alkylation of phenol with allylic alcohol is almost unexistent in the available literature.…”

Acid catalyzed alkylation of phenols with cyclohexene: Comparison between homogeneous and heterogeneous catalysis, influence of cyclohexyl phenyl ether equilibrium and of the substituent on reaction rate and selectivity

“…The mechanistic aspect of the electrophilic attack to the phenol is investigated from a theoretical point of view by Tang and coworkers. These authors suggested that the addition of the sulfonic acid to the olefins occurs leading to the formation of a sulfonic ester intermediate, which, in turns, reacts with phenol to form the products of alkylation [31].…”

Kinetics and mechanism of acid catalyzed alkylation of phenol with cyclohexene in the presence of styrene divinylbenzene sulfonic resins

“…These authors suggested that an olefin reacts with a sulfonic acid leading to the formation of a sulfonic ester intermediate, which, in turns, reacts with phenol to form the products of alkylation [25].…”