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

Abstract

Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/ co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O-methylated phenols and benzoic acids, and mono-C-methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide's neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Brønsted base.

Pd(II)-catalyzed carboxylation of aromatic C─H bonds with CO 2

“…4 ). This substrate was chosen because it can easily be produced from guaiacol ( 54 ), one of lignin’s main depolymerization products ( 55 ). The obtained product veratric acid ( 6 ) represents an important feedstock for pharmaceutical industry, for example, in the synthesis of the gastrointestinal drug itopride ( 56 ) and has antioxidant and anti-inflammatory activities itself ( 57 , 58 ).…”

Sustainable valorisation of renewables through dialkyl carbonates and isopropenyl esters

“…Differently substituted phenols, benzoic acids and arylacetonitrile substrates were selectively methylated applying this protocol (22 examples, yields up to > 99 %). 98 Li et al reported the first example of a phosgene-free, two-step sustainable methodology for the synthesis of carboxylic anhydrides (NCAs) from γ-benzyl-Lglutamate (BLG) and DMC, upon initial formation of the Nmethoxycarbonyl-γ-benzyl-L-glutamate intermediate (NOM-BLG, 84 % yield) followed by intramolecular cyclization to give NCA-BLG in 67 % yield. 99 In the last 5 years, DMC was the main DACs employed in chemical valorisation of bio-derived platform chemicals, developing novel effective and sustainable methylation protocols accessing both aromatic platform chemicals and/or valuable renewable based monomers (e.g.…”

“…Differently substituted phenols, benzoic acids and arylacetonitrile substrates were selectively methylated applying this protocol (22 examples, yields up to >99%). 98 Li et al reported the first example of a phosgene-free, two-step sustainable methodology for the synthesis of carboxylic anhydrides (NCAs) from γ-benzyl- l -glutamate (BLG) and DMC, upon initial formation of the N -methoxycarbonyl-γ-benzyl- l -glutamate intermediate (NOM-BLG, 84% yield) followed by intramolecular cyclization to give NCA-BLG in 67% yield. 99…”

Ultrasound‐Mediated Monodesulfonation of Polyphenol Sulfonate and One‐Pot Generation of Alkyl Aryl Ether under Solvent‐Free Conditions

“…[24] Methylation can also modify the solubility of drug molecules and improve the off-target selective as well. [25] The popular alkylation reagents, including alkyl halides, [26] dimethyl sulfates, [27] alkyl sulfonates [28,29] have been restricted for their environmental toxicity, potential danger to health and/or genotoxicity. [30][31][32][33][34] Safe and effective reagents are still in limited supply.…”