KEY CONCEPT
The more oxidized the functional group, the more reactive it is in both nucleophile–
electrophile and oxidation–reduction reactions.One common reactive site on the MCAT is the carbon of a carbonyl, which can be found in carboxylic
acids and their derivatives, aldehydes, and ketones. Within a carbonyl-containing compound, the
carbon of the carbonyl acquires a positive polarity due to the electronegativity of the oxygen. Thus,
the carbonyl carbon becomes electrophilic and can be a target for nucleophiles. Further, the α-
hydrogens are much more acidic than in a regular C–H bond due to the resonance stabilization of
the enol form. These can be deprotonated easily with a strong base, forming an enolate, as shown in
Figure 4.9. The enolate then becomes a strong nucleophile, and alkylation can result if good
electrophiles are available.
Figure 4.9. Enol and Enolate Forms of a KetoneA second reactive site for consideration is the substrate carbon in substitution reactions. SN 1
reactions, which have to overcome the barrier of carbocation stability, prefer tertiary to secondary
carbons as reactive sites, and secondary to primary. For SN2 reactions, which have a bigger barrier in
steric hindrance, methyl and primary carbons are preferred over secondary, and tertiary carbons
won’t react. This is all because of the mechanism of these two reactions.
STERIC PROTECTION
Steric hindrance describes the prevention of reactions at a particular location within a molecule
due to the size of substituent groups. For example, SN2 reactions won’t occur with tertiary
substrates. This characteristic of steric protection can be a useful tool in the synthesis of desired