Methanesulfonyl chloride is mainly used to give methanesulfonates by its reaction with alcohols in the presence of a non-nucleophilic base. In contrast to the formation of toluenesulfonates from alcohols and p-toluenesulfonyl chloride in the presence of pyridine, the formation of methanesulfonates is believed to proceed via a mechanism wherein methanesulfonyl chloride first undergoes an E1cb elimination to generate the highly reactive parent sulfene (), followed by attack by the alcohol and rapid proton transfer to generate the observed product. This mechanistic proposal is supported by isotope labeling experiments and the trapping of the transient sulfene as cycloadducts.
Methanesulfonates are used as intermediates in substitution reactions, elimination reactions, reductions, and rearrangement reactions. When treated with a Lewis acid, oxime methanesulfonates undergo facile Beckmann rearrangement.
Methanesulfonates are occasionally used as a protecting group for alcohols. They are stable to acidic conditions and is cleaved back to the alcohol using sodium amalgam.