82 Nucleophilic Aromatic Substitution
A nucleophilic substitution is a substitution reaction in organic chemistry in which the
nucleophile displaces a good leaving group, such as a halide on an aromatic ring. In order
to understand this type of reaction, it is important to recognize which chemical groups are
good leaving groups and which are not.
82.1 Leaving Groups.
Aleavinggroupcanprobablymostsimplybedescribedasanatomormoleculethatdetaches
from an organic molecule. The ability for a functional group to leave is calledlability.
Leaving groups affect the intrinsic reactivity of the molecule as a whole, but only until,
quite naturally, they actually leave.
The lower the pKaof the conjugate acid for a given leaving group, the better that leaving
group is at actually leaving. This is because such groups can easily stabilize any devel-
oping negative charge and without stabilization, a leaving group will actually become a
nucleophile causing the reaction to cycle pointlessly between attached and detached forms.
(This explains why a strong base is nearly always a poor leaving group.)
In room temperature water, the sequence of lability is:
- Less lability
- amine/amide (NH 2 - )
- alkoxy/alkoxide (RO-)
- hydroxyl/hydroxide (HO-)
- carboxylate (RCOO-)
- fluoro/fluoride (F-)
- water (H 2 O)
- chloro/chloride (Cl-)
- bromo/bromide (Br-)
- iodo/iodide (I-)
- azide (N 3 - )
- thiocyanate (SCN-)
- nitro/nitrite (NO 2 )
- cyano/cyanide (CN-)
- Greater Lability