Electrophilic Aromatic Substitution in Preparation
Nitration reactions represent one of the classic electrophilic aromatic substitution reactions. Nitration has been
used extensively as a means of introducing the
substituent (via a nitronium ion) on an aromatic ring. The
nitro group may then be reduced to an amino group. Upon diazotization of the amino with nitrous acid, an
excellent leaving group has been introduced onto the ring. This group may be displaced by a number of nuc1e-
ophiles, furnishing an excellent synthetic route to a number of different molecules.
The nitro group is strongly deactivating. As a result, nitration usually stops at the mono-substituted product.
However, if there are activating groups also present on the ring, then the reaction may proceed to the all-sub-
A number of reaction conditions have been developed over the years to generate the nitronium ion. The clas-
sic method is the use of sulfuric acid, concentrated nitric acid, and heat. However, anhydrous nitric acid may
also be used as in the present reaction. Fuming nitric acid and red fuming nitric acid have also been used in
situations where the reaction has not been possible with milder acids. Both white fuming and red fuming nitric
acid contain dissolved nitrogen dioxide, which produces an acid that is greater than 90% nitric acid; concen-
trated nitric acid is an azeotrope composed of 68-70% nitric acid and the remainder water.
"Milder" conditions can be employed by using nitric acid absorbed on silica gel and other agents that have a
nitronium ion to donate in the course of a reaction. With these methods, there are fewer decomposition prod-
ucts and no strong acids to do deal with, making the isolation of the product easier. Other acids besides sulfu-
ric acid, such as acetic acid or polyphosphoric acid, can be employed, which represent milder conditions also.
Because nitric acid is a strong oxidizing agent, side reactions are common in oxidation procedures. Susceptible
molecules, e.g., ferrocene, undergo decomposition and/or oxidation before nitration can occur.
Two nitration reactions are given. In the current reaction, nitration of p-dichlorobenzene stops with
the addition of one nitro group and uses anhydrous nitric acid as the nitrating agent. The second reaction
is the nitration of phenol using nitric acid-treated silica gel. This reaction results in a mixture of three
products: 2-nitrophenol, 2,4-dinitrophenol, and 4-nitrophenol. These products are separated using column
chromatography. In the first case, the chloro groups are deactivating, and the molecule is further deactivated
by the nitro group so that only one product is formed. In the second case, the phenol is a strongly activating
group, and at least two products are possible:
and p-nitrophenol. A third product results when a second nitro-
nium ion attacks the unoccupied
position on one of