leaving group
Summary
A leaving group is the atom or group that departs with the bonding electron pair from the substrate in substitution and elimination reactions. Good ones are generally weak bases, the conjugate bases of strong acids (I⁻ > Br⁻ > Cl⁻ > F⁻, tosylate, H₂O); OH⁻ and NH₂⁻ are poor.
Detail
Meaning: A leaving group is the atom or group that departs from the substrate carbon, taking the bonding electron pair with it, in SN1, SN2, E1 and E2 reactions and in nucleophilic acyl substitution. A good leaving group is stable once it leaves, which generally means it is a weak base, the conjugate base of a strong acid. I⁻, Br⁻, Cl⁻, tosylate and neutral H₂O are good; OH⁻, OR⁻ and NH₂⁻ are poor.
On the MCAT: Passages ask you to rank substrates by reactivity (an alkyl iodide reacts faster than the alkyl chloride in SN1 and SN2, other factors equal) or to choose a step that makes a poor leaving group usable: protonate an alcohol with strong acid so it leaves as H₂O, or convert it to a tosylate or mesylate. For carboxylic acid derivatives, reactivity toward nucleophilic acyl substitution follows leaving group ability: acid chloride > anhydride > ester > amide.
Common confusion: Students pick fluoride because F is the most electronegative halogen. But HF is the weakest hydrogen halide acid, so F⁻ is the strongest base of the halides and the poorest leaving group. Compare conjugate acid pKa values: a lower pKa means a better leaving group.
Sources
- Organic Chemistry (Wade)
- Organic Chemistry (McMurry)
- Organic Chemistry (Klein)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.