Direct Phenolysis Reactions of Unactivated Amides into Phenolic Esters Promoted by a Heterogeneous CeO2 Catalyst

Abstract

The direct catalytic esterification of amides that leads to the construction of C-O bonds through the cleavage of amide C-N bonds is a highly attractive strategy in organic synthesis. While aliphatic and aromatic alcohols can be readily used for the alcoholysis of activated and unactivated amides, the introduction of phenols is more challenging due to their lower nucleophilicity in the phenolysis of unactivated amides. Herein, we demonstrate that phenols can be used for the phenolysis of unactivated amides into the corresponding phenolic esters using a simple heterogenous catalytic system based on CeO₂ under additive-free reaction conditions. The method tolerates a broad variety of functional groups (>50 examples) in the substrates. Results of kinetic studies afforded mechanistic insights into the principles governing this reaction, suggesting that the cooperative effects of the acid-base functions of catalysts would be of paramount importance for the efficient progression of the C-N bond breaking process, and consequently, CeO₂ showed the best catalytic performance among the catalysts explored.

Keywords: acid-base cooperation; heterogeneous catalysts; phenolic esters; phenolysis; unactivated amides.