The alcohol is the most common functional group in organic chemistry — and one of the worst leaving groups. Attach its oxygen to a sulfonyl group and that same carbon suddenly rivals bromide and iodide.
Same C–O carbon, three fates: as an alcohol it is inert, but as a sulfonate ester it is primed to react. Structures drawn live.
1. The Hydroxyl Group Must Be Activated Because Hydroxide Is a Terrible Leaving Group
Hydroxide is a strong base (pKa of water ≈ 15.7), so it clings to carbon and R–OH won't do a plain SN2.
2. TsCl Gives a Tosylate and MsCl Gives a Mesylate — the C–O Bond Is Never Touched
The alcohol oxygen attacks sulfur and chloride leaves: TsCl/pyridine gives –OTs, MsCl/Et3N gives –OMs, all without breaking the C–O bond.
Ethanol → ethyl tosylate. Swap TsCl/pyridine for MsCl/Et3N to get the mesylate instead.
3. A Sulfonate Is a Weak Base, So It Is an Excellent Leaving Group
Sulfonic acids are strong (TsOH pKa ≈ −2.8), so their conjugate bases are weak, delocalized, and leave readily: –OTf > –OMs ≈ –OTs > I– > Br– ≫ –OH.
Leaving-group comparison: sulfonate esters sit right alongside — or above — the good alkyl halides.
4. Once Made, R–OTs Does SN2, SN1, or E2 Just Like an Alkyl Halide
A tosylate is a "super halide" that plugs into any substitution or elimination — azide gives an alkyl azide, cyanide extends the chain to a nitrile.
Ethyl tosylate + azide → ethyl azide by a clean SN2 displacement of –OTs.
Cyanide displaces the tosylate to build a new C–C bond, giving a nitrile (propanenitrile).
5. Making the Tosylate Retains Configuration; the SN2 Then Inverts It
Sulfonylation never touches the stereocenter (retention), while the following backside SN2 inverts it — so the overall sequence gives defined net inversion.
(S)-2-butanol → its tosylate with retention — the C–O carbon is never touched.
6. Summary
–OH is a bad leaving group · TsCl/pyridine → –OTs, MsCl/Et3N → –OMs, –OTf most reactive · sulfonates are weak bases from strong acids · activation retains configuration · the SN2 then inverts · net: alcohol → tosylate → substitution with defined inversion.
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Direct SN2 would require expelling hydroxide (–OH), a strong base and a terrible leaving group, so nothing happens. Converting the alcohol to ethyl tosylate with TsCl/pyridine replaces –OH with –OTs, the weak, stable conjugate base of a strong sulfonic acid. Now cyanide displaces the sulfonate easily to give the nitrile — the leaving group changed, the carbon did not.
A leaving group departs as a base, and weaker bases leave better. –OH is the conjugate base of water (pKa ≈ 15.7) — a strong base. –OTs is the conjugate base of p-toluenesulfonic acid (pKa ≈ −2.8), a strong acid — so its conjugate base is very weak and stabilized by delocalization over three oxygens. Weak base = excellent leaving group.
Tosylate formation happens only at oxygen — the C–O bond is never broken — so configuration is retained; the tosylate has the same spatial arrangement as the alcohol. The subsequent SN2 is a backside attack, which inverts the stereocenter. Net over the two steps: inversion, but by a fully predictable path.
–OTf > –OMs ≈ –OTs > I– > Br– ≫ –OH. The three sulfonates are all excellent because they come from strong acids (triflic > methanesulfonic ≈ toluenesulfonic). Reagents: TsCl with pyridine makes the tosylate; MsCl with Et3N makes the mesylate.
Draw this on the whiteboard
Open the OChem Board whiteboard — benzene rings, wedge/dash bonds, and a clickable periodic table built in. No account needed.