MeOTf

MeOTf, or methyl triflate, is a highly reactive methylating agent used in organic synthesis. It is a colorless, moisture-sensitive liquid in which a methyl group is bound to a triflate leaving group (trifluoromethanesulfonate).

Reaction and mechanism: The triflate anion (CF3SO3−) is an excellent leaving group, making MeOTf a strong electrophile. Nucleophiles such as alcohols, phenols, amines, and thiols can attack the methyl carbon in an SN2 process, displacing triflate and forming methylated products. Because of its high reactivity, MeOTf can methylate weak nucleophiles, but it requires strictly dry conditions and often low temperatures to minimize side reactions and decomposition.

Applications: MeOTf is used to convert alcohols and phenols into methyl ethers, to quaternize amines by N-methylation and subsequent ammonium salt formation, and to generate methyl esters from carboxylates. It is valued for rapid methylation and for enabling transformations that are difficult with less reactive methylating agents. It is commonly employed in pharmaceutical synthesis, materials chemistry, and other areas of organic synthesis where strong, selective methylation is required.

Preparation and handling: MeOTf is commercially available and routinely used under an inert, dry atmosphere. It is typically stored in dry, tightly sealed containers away from moisture. Handling requires a fume hood, appropriate personal protective equipment, and procedures suitable for reactive, moisture-sensitive reagents.

Safety: MeOTf is highly corrosive and toxic, with substantial inhalation and dermal hazards. It reacts vigorously with water and alcohols, generating heat and corrosive byproducts. Proper containment, ventilation, and rapid quenching of spills are essential when working with this reagent.