Electrophilic Aromatic Substitution
83.3.1 Electrophilic aromatic halogenation
Figure 174 Electrophilic aromatic substitution of benzene
Another important reaction of benzene is the electrophilic substitution of halides, a specific
type of electrophililc aromatic substitution. These reactions are very useful for adding sub-
stituents to an aromatic system. The rates of the reactions increase with the electrophilicity
of the halogen: hence, fluorination in this manner is too rapid and exothermic to be prac-
tical, whereas iodine requires the most vigorous conditions. Chlorination and bromination
are the most often practiced in the lab of the four possible halogenations. Halobenzenes
are used for pesticides, as well as the precursors to other products. Many COX-2 inhibitors
contain halobenzene subunits.
Some highly activated aromatic compounds, such as phenol and aniline, are reactive enough
toundergohalogenationwithouta catalyst, butfortypicalbenzenederivatives(andbenzene
itself), the reactions are extremely slow at room temperature in the absence of a catalyst.
Usually, Lewis acids are used as catalysts, which work by helping to polarize the halogen-
halogen bond, thus decreasing the electron density around one halogen atom, making it
more electrophilic. The most common catalysts used are either Fe or Al, or their respective
chlorides and bromides (+3 oxidation state). Iron(III) bromide and iron(III) chloride lose
theircatalyticactivityiftheyarehydrolyzedbyanymoisturepresent, includingatmospheric
water vapor. Therefore, they are generated in situby adding iron fillings to bromine
or chlorine. Iodination is carried out under different conditions: periodic acid is often
used as a catalyst. Under these conditions, the I+ ion is formed, which is sufficiently
electrophilic to attack the ring. Iodination can also be accomplished using a diazonium
reaction. Fluorination is most often done using this technique, as the use of fluorine gas is
inconvenient and often fragments organic compounds.
Halogenation of aromatic compounds differs from the additions to alkenes or the free-radical
halogenations of alkanes, which do not require Lewis acid catalysts. The formation of the
arenium ion results in the temporary loss of aromaticity, the overall result being that the
reaction’s activation energy is higher than those of halogenations of aliphatic compounds.
Halogenation of phenols is faster in polar solvents due to the dissociation of phenol, because
the phenoxide (-O-) group is more strongly activating than hydroxyl itself.
83.3.2 Electrophilic aromatic sulfonation
Aromaticsulfonationisanorganicreactioninwhichahydrogenatomonanareneisreplaced
by a sulfonic acid functional group in an electrophilic aromatic substitution.
The electrophile of such a reaction is sulfur trioxide (SO 3 ), which can be released from
oleum (also known as fuming sulfuric acid), essentially sulfuric acid in which gaseous sulfur
trioxide has been dissolved.
In contrast to aromatic nitration and other electrophilic aromatic substitutions, aromatic
sulfonation is reversible. Sulfonation takes place in strongly acidic conditions, and desul-
fonation can occur on heating with a trace of acid. This also means that thermodynamic,