Masked N‐Heterocyclic Carbene‐Catalyzed Alkylation of Phenols with Organic Carbonates

Abstract

An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs.

Glycolysis of PET Using 1,3-Dimethylimidazolium-2-Carboxylate as an Organocatalyst

“…48 Furthermore, the mechanism of transesterification of diols with dimethylcarbonate catalyzed by 1,3-dialkylimidazolium-2-carboxylates has been explained by Naik et al, 61,62 and Stewart et al 37 through in situ decarboxylation of the 1,3-dialkylimidazolium-2carboxylates to NHCs that initiate nucleophilic attack. Lui et al 66 have also invoked a masked-carbene mechanism for alkylation of phenols with 1,3-dialkylimidazolium-2-carboxylates.…”

A New Alkylation of Aryl Alcohols by Boron Trifluoride Etherate

“…p-Chloroanisole 14 [30]: colourless liquid, 0.82 g (75%); 1 H NMR (400 MHz, Chloroform) δ 7.24 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 3.78 (s, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 158.10, 129.23, 125.43, 115.06, 55.40.…”

Methylation with Dimethyl Carbonate/Dimethyl Sulfide Mixtures: An Integrated Process without Addition of Acid/Base and Formation of Residual Salts

“…This afforded methylation products of good purity, as confirmed by NMR spectroscopy, GC, or melting point measurements. In some cases, these products were colorless liquids/solids (Figure S1) that required no further purification (i. e., by column chromatography for methylation using heterogeneous bases [32] such as MgO and homogeneous ones [33,34,41] such as DBU). In other examples, the products could be decolorized by passing their solutions through a short plug of silica, during which the loss of mass was negligible.…”

“…In contrast, more laborious procedures (e. g., neutralization, filtration, and extractions with additional solvents) are required to isolate the products from other methylation processes, especially those that utilize homogeneous catalysts, such as DBU. [33,34,41] Thus, our methylation process effectively minimizes the generation of chemical waste.…”

“…[20] Brønsted bases are typically used as catalysts in the methylation of phenols with DMC. [4,[21][22][23][24][25][26][27][28][29][30][31][32][33][34] This methylation normally proceeds akin to an S N 2 Williamson reaction (Scheme 1). Similarly, Brønsted bases are typically used as catalysts for the mono-C-methylation of arylacetonitriles and arylacetoesters with DMC.…”