459-60-9Relevant articles and documents
Cu-Catalyzed Phenol O-Methylation with Methylboronic Acid
Bartlett, Mairead E.,Chavez, Angela K.,Gaffney, Uma Bhagwat,Gorin, David J.,Lee, Joyce,Sharew, Betemariam,Wu, Miranda,Zhu, Yingchuan
supporting information, p. 5661 - 5664 (2021/11/11)
A Cu-catalyzed oxidative cross-coupling of phenols with methylboronic acid to form aryl methyl ethers has been developed, expanding the scope of Chan-Evans-Lam alkylation. Electron-deficient phenol derivatives with a broad array of functional groups are methylated in high yields. Increased reaction temperature and catalyst loading enables the methylation of substrates incorporating pyridine and dihydroquinolone motifs. Electron-rich phenol derivatives are poor substrates for the methylation; the characterization of C?H homodimerization products formed from these substrates illuminates a competing mechanistic pathway.
Trialkylammonium salt degradation: Implications for methylation and cross-coupling
Assante, Michele,Baillie, Sharon E.,Juba, Vanessa,Leach, Andrew G.,McKinney, David,Reid, Marc,Washington, Jack B.,Yan, Chunhui
, p. 6949 - 6963 (2021/06/02)
Trialkylammonium (most notably N,N,N-trimethylanilinium) salts are known to display dual reactivity through both the aryl group and the N-methyl groups. These salts have thus been widely applied in cross-coupling, aryl etherification, fluorine radiolabelling, phase-transfer catalysis, supramolecular recognition, polymer design, and (more recently) methylation. However, their application as electrophilic methylating reagents remains somewhat underexplored, and an understanding of their arylation versus methylation reactivities is lacking. This study presents a mechanistic degradation analysis of N,N,N-trimethylanilinium salts and highlights the implications for synthetic applications of this important class of salts. Kinetic degradation studies, in both solid and solution phases, have delivered insights into the physical and chemical parameters affecting anilinium salt stability. 1H NMR kinetic analysis of salt degradation has evidenced thermal degradation to methyl iodide and the parent aniline, consistent with a closed-shell SN2-centred degradative pathway, and methyl iodide being the key reactive species in applied methylation procedures. Furthermore, the effect of halide and non-nucleophilic counterions on salt degradation has been investigated, along with deuterium isotope and solvent effects. New mechanistic insights have enabled the investigation of the use of trimethylanilinium salts in O-methylation and in improved cross-coupling strategies. Finally, detailed computational studies have helped highlight limitations in the current state-of-the-art of solvation modelling of reaction in which the bulk medium undergoes experimentally observable changes over the reaction timecourse. This journal is
Methylation with Dimethyl Carbonate/Dimethyl Sulfide Mixtures: An Integrated Process without Addition of Acid/Base and Formation of Residual Salts
Chan, Bun,Lui, Matthew Y.,Lui, Yuen Wai
, (2022/01/08)
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 Br?nsted base.
