mesylate

Meaning: A mesylate is the methanesulfonate group, CH₃SO₂O–, often written OMs. It is the conjugate base of methanesulfonic acid, a very strong acid (pKa about −2), so it is a very weak base and an excellent leaving group. Its negative charge is delocalized by resonance over three oxygens. An alcohol's OH is a poor leaving group because OH⁻ is a strong base. Converting ROH to ROMs makes substitution or elimination possible.

Equation: ROH + CH₃SO₂Cl → ROSO₂CH₃ + HCl, where ROH is the alcohol, CH₃SO₂Cl is methanesulfonyl (mesyl) chloride, and ROSO₂CH₃ is the mesylate. A base such as pyridine or triethylamine takes up the HCl.

On the MCAT: A passage shows an alcohol converted to a mesylate (or tosylate), then treated with a nucleophile. Predict the stereochemistry: mesylation leaves the C–O bond intact, so configuration at the carbon is retained. A following SN2 attack from the back side inverts it, so the overall result from alcohol to product is inversion. With a strong base, the mesylate can instead undergo E2. Mesylate and tosylate are similar leaving groups, and triflate is better still.

Common confusion: Students think forming the mesylate inverts the stereocenter. It does not, because the alcohol oxygen attacks sulfur, not carbon. Inversion happens only in the later SN2 step. Also, mesylate is the leaving group, not the nucleophile.