Figure 4.4. Comparisons of ElectrophilicityThe carboxylic acid derivatives are often ranked by electrophilicity. Anhydrides are the most
reactive, followed by carboxylic acids and esters, and then amides. In practical terms, this means
that derivatives of higher reactivity can form derivatives of lower reactivity but not vice-versa,
similar to the acid–base reactions described previously.
LEAVING GROUPS
Leaving groups are the molecular fragments that retain the electrons after heterolysis. Heterolytic
reactions are essentially the opposite of coordinate covalent bond formation: a bond is broken and
both electrons are given to one of the two products. The best leaving groups will be able to stabilize
the extra electrons. Weak bases are more stable with an extra set of electrons and therefore make
good leaving groups. By this logic, the conjugate bases of strong acids (like I–, Br–, and Cl–) tend to
make good leaving groups. Leaving group ability can be augmented by resonance and by inductive
effects from electron-withdrawing groups: these help delocalize and stabilize negative charge.
Alkanes and hydrogen ions will almost never serve as leaving groups because they form very
reactive, strongly basic anions. We can think of leaving groups and nucleophiles as serving opposite
functions. In substitution reactions, the weaker base (the leaving group) is replaced by the stronger
base (the nucleophile).