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

Abstract

a b s t r a c tThe reactivity of several phenols toward liquid phase alkylation with cyclohexene in the presence of heterogeneous and homogeneous acid catalyst at 358 K is studied. The comparison between Amberlyst 15 and CH 3 SO 3 H, as examples of heterogeneous and homogeneous systems, shows a higher activity of the former with different behavior of selectivity between the two systems, anyway, in both systems O-alkylation and ring alkylations occur. A remarkable difference in the selectivity of the ring alkylation between heterogeneous and homogeneous systems is observed: Amberlyst 15 shows a constant ortho/para ratio close to 2, while in the presence of CH 3 SO 3 H ortho/para is variable from 3 to 5, suggesting an involvement of the cyclohexyl phenyl ether rearrangement. This is proved also by a direct relationship between the ortho/para ratio and the concentration of the cyclohexyl phenyl ether when CH 3 SO 3 H is used as a catalyst. The formation of cyclohexyl aryl ethers is reversible; on the contrary, ring alkylation appears irreversible. The reactivity of the dimethylphenols shows a strong influence of the steric hindrance of the substituent on the electrophilic attack of the cyclohexyl cation, which is poorly influenced by the inductive effect of the methyl group.

Mechanism of Phenol Alkylation in Zeolite H-BEA Using In Situ Solid-State NMR Spectroscopy

“…Alkylation of phenols with olefins and alcohols has been extensively studied, in vapor and liquid phases, over a wide range of solid catalysts. − ,− The hypothesized mechanisms from these experimental studies were, however, seldom based on rigorous rate measurements and direct spectroscopic evidence, but rather, almost always “borrowed”/adapted from the classical Friedel–Crafts alkylation chemistry in a homogeneous phase, or inferred from insufficient and less informative ex situ analyses of reaction products. In particular, for Brønsted acidic zeolites, the mechanism for phenol alkylation with alcohol (e.g., methanol, tert -butyl alcohol) is significantly more controversial, compared to phenol alkylation with olefin (e.g., propene, 1-octene).…”

Iridium-Catalyzed, Intermolecular Hydroetherification of Unactivated Aliphatic Alkenes with Phenols

“…However, these additions often require strong acids and high temperatures, form side products from isomerization of carbocationic intermediates, and occur without control of the product stereochemistry. Moreover, acid-catalyzed additions of phenols to alkenes occur with competitive reaction of the alkene at the O–H bond and at an ortho or para C–H bond . Metal-catalyzed hydroetherification would exploit the abundance and stability of alkene starting materials and could overcome many of the limitations of the classical syntheses of ethers.…”

Electrocatalytic Radical-Polar Crossover Hydroetherification of Alkenes with Phenols

“…[24] Moreover, acid-catalyzed additions suffer from competitive chemoselectivity between forming the C−O bond and undesired C−C bond with ortho or para C−H bond of phenols. [25][26][27] In this context, catalytic hydroetherification of a wide range of alkenes with phenols as the nucleophile is particularly attractive due to the accessibility to hindered alkyl aryl ethers but remains to be scarce. [18,28] In addition, this approach has yet been compatible to synthesize key structural motifs in bioactive and pharmaceutical compounds.…”