9.2 Reactivity Principles

LEARNING GOALS

After   Chapter 9.2,    you will    be  able    to:

Order   carboxylic  acid    derivatives,    including   anhydrides, esters, and amides, based   on  their

reactivity

Explain the relatively  high    rate    of  hydrolysis  in  β-lactams

Identify    the properties  of  the carboxylic  acid    derivatives that    cause   their   reactivities    to

differ

Regardless of the carboxylic acid derivative at hand, there are some rules that govern the reactivity
of these molecules.

RELATIVE REACTIVITY OF DERIVATIVES

In a nucleophilic substitution reaction, the reactivity of the carbonyl is determined by its
substituents. Anhydrides are most reactive, followed by esters (which are essentially tied with
carboxylic acids), then finally amides. This can be explained by the structure of these molecules.
Anhydrides, with their resonance stabilization and three electron-withdrawing oxygen atoms, are
the most electrophilic. Esters, by comparison, lack one electron-withdrawing carbonyl oxygen and
are slightly less reactive. Finally, amides, with an electron-donating amino group, are the least
reactive toward nucleophiles.

KEY CONCEPT