CH3SO2Cl

CH3SO2Cl, methanesulfonyl chloride (mesyl chloride), is a reactive sulfonylating agent used in organic synthesis. It is a moisture-sensitive, lachrymatory liquid that hydrolyzes upon contact with water to methanesulfonic acid and hydrogen chloride.

Preparation and handling: It is typically prepared by chlorination of methanesulfonic acid (CH3SO3H) with reagents such as thionyl chloride (SOCl2) or phosphorus pentachloride (PCl5), generating CH3SO2Cl, sulfur dioxide, and HCl. It is corrosive and should be stored in tightly closed containers under dry, inert conditions, away from moisture and bases, and handled in a fume hood with appropriate personal protective equipment.

Reactions and uses: In the presence of a base, methanesulfonyl chloride reacts with alcohols to give the corresponding methylsulfonate esters (mesylates), R-O-SO2-CH3, which are excellent leaving groups for nucleophilic substitution. It also reacts with amines to form sulfonamides (R-NH-SO2-CH3). These mesylation steps activate substrates for SN1/SN2 reactions and are widely used to convert poor leaving groups into good ones in medicinal chemistry and natural product synthesis. Methanesulfonyl chloride can also serve as a reagent in certain protecting group strategies, though tosyl and nosyl groups are more commonly used for amine protection.

Safety and environmental considerations: CH3SO2Cl is a corrosive, irritant chemical. It reacts vigorously with water, releasing heat and corrosive acids. Proper waste handling and disposal according to institutional and regulatory guidelines are required.