tosylate
Summary
A tosylate is the ester of an alcohol with p-toluenesulfonic acid (R–OTs). It converts a poor leaving group, OH⁻, into an excellent one, the tosylate anion, so the carbon can undergo SN2 (or E2) reactions. Tosylation keeps the carbon's configuration.
Detail
Meaning: A tosylate (OTs) is the group R–O–SO₂–C₆H₄–CH₃, made by treating an alcohol with tosyl chloride (TsCl) and a base such as pyridine. Hydroxide is a strong base and a poor leaving group. The tosylate anion is the conjugate base of a strong acid (p-toluenesulfonic acid, pKa about −3 to −2), and its negative charge is delocalized by resonance over three oxygens. It is therefore a very weak base and an excellent leaving group.
On the MCAT: A passage converts an alcohol to a tosylate, then adds a nucleophile (CN⁻, N₃⁻, I⁻, RS⁻) to give a substitution product. For a chiral secondary alcohol, tosylation does not touch the stereocenter, because the C–O bond is not broken. The following SN2 step then inverts the configuration. With a strong, bulky base, the tosylate can instead undergo E2 elimination. You may be asked to rank leaving groups (OTs, I⁻, Br⁻, Cl⁻ are good; OH⁻, NH₂⁻, OR⁻ are poor) or to name the reagents. Mesylate (OMs) and triflate (OTf) work the same way, and triflate is even better.
Common confusion: Students think tosylation inverts the stereocenter. It retains configuration, because the alcohol's O–H bond reacts and the C–O bond stays intact. Inversion happens only in the later SN2 step. Do not confuse the tosylate leaving group (OTs) with tosyl chloride (TsCl), which is the reagent that installs it.
Sources
- Organic Chemistry (Clayden)
- Organic Chemistry (Wade)
- Organic Chemistry (Klein)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.