Organic Chemistry

Nucleophilic Substitution Reactions

Another important point to keep in mind, and this can be seen clearly in the example above,
during anSN2 reaction, the molecule undergoes an inversion. The bonds attached to the
α-carbon are pushed away as the nucleophile approaches. During the transition state, these
bonds become planar with the carbon and, as the bromine leaves and the nucleophile bonds
to the α-carbon, the other bonds fold back away from the nucleophile. This is particularly
important in chiral^2 or pro-chiral molecules, where an R configuration will be converted
into an S configuration and vice versa. As you’ll see below, this is in contrast to the results
ofSN1 reactions.

Examples:

OH-+ CH 3 —Cl → HO—CH 3 + Cl-

OH- is the nucleophile, Cl is the electrophile, HOCH3 is the product, and Cl- is the leaving
group.

or,

Na+I-+ CH 3 -Br → I-CH 3 + Na+Br-

The above reaction, taking place in acetone as the solvent, sodium and iodide disassociate
almost completely in the acetone, leaving the iodide ions free to attack the CH-Br molecules.
The negatively charged iodide ion, a nucleophile, attacks the methyl bromide molecule,
forcing off the negatively charged bromide ion and taking its place. The bromide ion is the
leaving group.

Nucleophilicity

Nucleophilicity is the rate at which a nucleophile displaces the leaving group in a reaction.
Generally, nucleophilicity is stronger, the larger, more polarizable, and/or the less stable
the nucleophile. No specific number or unit of measure is used. All other things being
equal, nucleophiles are generally compared to each other in terms of relative reactivity. For
example, a particular strong nucleophile might have a relative reactivity of 10,000 that of
a particular weak nucleophile. These relationships are generalities as things like solvent
and substrate can affect the relative rates, but they are generally good guidelines for which
species make the best nucleophiles.

All nucleophiles are Lewis bases^3. InSN2 reactions, the preferred nucleophile is a strong
nucleophile that is a weak base. Examples of these are N 3 - , RS-, I-, Br-, and CN-.

Alternatively, a strong nucleophile that’s also a strong base can also work. However, as
mentioned earlier in the text, sometimes reaction mechanisms compete and in the case of
a strong nucleophile that’s a strong base, theSN2 mechanism will compete with theE2
mechanism. Examples of strong nucleophiles that are also strong bases, include RO-and
OH-.

List of descending nucleophilicitiesI-> Br-> Cl->> F-> -SeH > -OH > H 2 O

2 Chapter 32 on page 129
3 Chapter 11 on page 51