Nucleophilic Substitution Reactions

Neutral or anionic Lewis bases are nucleophilic. Typical nucleophiles are RO:-, RS:-, R3N:and
R3P:. They can displace the same or other Lewis bases from carbon in an organic molecule, RX.
The displaced Lewis base is called a leaving group. Halide ions, X:-, are typical leaving groups.
Weak bases are good leaving groups.Halides ions being the conjugate bases of strong acids are
therefore good leaving groups. Which halide is the best leaving group?

The general reaction scheme for each process is shown below. Note that charge is conserved (i.e.
it is equal on each side).

Anionic base:

Nu

+

R

X

R

Nu

+

X

Neutral base:

Nu

+

R

X

R

Nu

+

X

The mechanism for the nucleophilic substitution reaction is determined using two important tools,
reaction kineticsand stereochemistry. Each of these tools tells us something about how the
reaction occurs. The reaction kinetics tells us how many molecules are involved in the transition
state of the rate determining step. The stereochemistry reveals the structure of the transition state in
this step.

Kinetics

To study the kinetics of a reaction we need to determine the rate of the reaction and which
molecules influence the rate. This is simply done by measuring the rate as a function of the
concentration of each reactant.

•

Bimolecular reactions - reactions involving 2 molecules in the rate determining step - are
called SN2 reactions.

Stereochemistry

To study the stereochemistry of the reaction we need to work withchiral molecules. The
stereochemistry of a reaction refers to the relative configurations of the leaving group and the
nucleophile bonded to a stereocenter in the reactant and product, respectively. Note that the change
in stereochemistry can only be observed if the substrate is chiral.

•

SN2 reactions occur with inversion of configuration.