A Continuous Base-Catalyzed Methylation of Phenols with Dimethyl Carbonate

Abstract

We have found that the use of a conventional, heated, standard 316 stainless steel or steel-braided PTFE tube reactor is a good and easily scalable alternative to the use of continuous microwave-heated reactors. The heat-up is almost as fast as with microwave heating, and the reactors can easily be scaled towards large-scale production. The transfer of the reported microwave procedure to the continuous flow method went very smoothly, and we found that we could further optimize the reaction to a catalytic procedure where only 10 mol % of DBU is needed with only 3 equiv of DMC. The reaction can be run neat in cases where the starting material is soluble in DMC as phenol is, or with a small amount of DMF (2–3 vol). The reaction is efficient for different types of phenols, giving a clean reaction in high yields.

Recent advances in dialkyl carbonates synthesis and applications

“…1,370,371 Tundo et al have overviewed the reactivity of some soft/hard mono and bidentate nucleophiles at N, O, and S with DMC and analyzed the effect of their nature on discrimination between the C atoms of DMC. 371 In the published literature, they have shown good reactivity and selectivity with a number of nucleophilic substrates, such as phenols, [372][373][374][375][376][377][378] alcohols, [379][380][381] carboxylic acids, 378,[381][382][383] primary amines, 384 indole, 385 alkenes, 386 etc. Taking account of the large amount of literature about DMC application as an intermediate in organic synthesis, we present a brief introduction from the two aspects of carboxymethylation and methylation reaction.…”

“…13 Moreover, DMC has been proved as a more efficient methylating agent than MeOH at low temperature. 424 At the present time, the main catalysis systems are gas-liquid phase-transfer catalysts, 425 organotin, 374 ILs, 375,376,426,427 basic zeolites, [428][429][430] mixed oxides, hydrotalcite 378,424 and MOFs. 384 In order to realize a highly selective transformation, different continuous processes have been proposed by several groups, and the target product (e.g.…”

“…anisole) exhibited an excellent selectivity at a substantially quantitative conversion of the substrate. 375,376,431 (42)…”

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

“…The O-methylation of phenols is particularly significant, as aryl methyl ethers are valuable intermediates for the production of fine chemicals for use in organic synthesis. [1][2][3][4] In addition, phenyl methyl ether (anisole) is a green solvent [5][6][7][8][9] that is ranked highly in solvent selection guides. [10,11] Methylation has been applied to upgrade or stabilize biomass pyrolysis oil, [3,12] which contains a significant concentration of lignin-derived phenolic compounds.…”

“…[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.…”