Chemistry Reference
In-Depth Information
Figure 3.6 Steric effects can override the influence of pK
a
values on nucleophilicity.
to allow the nucleophile to react. In fact, it is this effect that can differentiate between a
reactive nucleophile and a true base. Consider the alkoxide ions illustrated in Figure 3.6.
If we take into account only the pK
a
values listed, we may expect that nucleophilicity
would increase as we move from methoxide to ethoxide to isopropoxide to tert-butoxide.
However, if we look at these conjugate bases not as a function of their corresponding
pK
a
values but as a function of their overall structure, we find a very different story.
Specifically, a methyl group is small compared to an ethyl group. Furthermore, an ethyl
group is small compared to an isopropyl group. Finally, an isopropyl group is small com-
pared to a tert-butyl group. Therefore, if we consider that increasing molecular volume
around a nucleophilic atom results in decreasing nucleophilicity, it is easy to reconcile
the trend illustrated in Figure 3.6. Furthermore, when a nucleophilic atom becomes steri-
cally blocked from acting as a nucleophile, the basic characteristics of this atom
becomes manifested. In fact, tert-butoxide anions are commonly used as bases in
organic chemistry due to the diminished nucleophilicity surrounding the oxygen. Finally,
it is important to remember that this effect is generally applicable to all nucleophiles
regardless of the atoms involved.
3.3 LEAVING GROUPS
No discussion of nucleophiles would be complete without addressing leaving groups. As
mentioned in Chapter 1 and illustrated in Scheme 3.12, leaving groups are important com-
ponents in nucleophilic reactions because they represent the molecular fragment that
