O-methylation of Hydroxyl-containing Organic Substrates: A Comprehensive Overview

In several cases, the occurrence of methylation on oxygen site of an organic molecule is not a straightforward process. Most of the O-methylations take place with hydroxyl groups of carboxylic acids, phenols, and alcohols, affording methyl esters, aryl methyl ethers, and alkyl methyl ethers, respectively. Polysaccharides are polyhydric alcohols that have received special interest for methylation purpose. A number of methylating agents have been employed to affix methyl group to molecule matrix via oxygen atom, and are, to cite but a few, methanol, methyl iodide, diazomethane, dimethyl sulfate, dimethyl carbonate, methyl triflate, tetramethylammonium salts and trimethyl phosphate. To the variety of existing OH-substrates and methylating agents, the myriad of organic and inorganic substances that play key roles in catalyzing the methylation reactions are added. The odd-even effect of acidic/basic character of a catalyst promotes the selectivity of methylation, hence the desired product. In most cases, every couple of catalyst/methylating agent brings about the O-methylation of the substrate through a unique mechanism.