Jasperse Chem 365
Nitration Lab
1
NITRATION OF METHYL BENZOATE
General Issues with Electrophilic Aromatic Substitution Reactions:
Aromatic substitution reactions involve the substitution of one (or more) aromatic
hydrogens with electrophiles. Two major synthetic issues are always involved.
1. Monosubsitution versus Polysubstitution
• Because there is more than one benzene hydrogen available, can the reaction be
disciplined so that monosubstition occurs rather than polysubstitution?
• Selective monosubstition is possible only if the monosubstitution product is less
reactive than the original reactant. If the reactivity of the monosubstitution product
equals or exceeds that of the original reactant, the monosubstitution product(s) will
proceed on to polysubstitution products.
• There are two reasons why a monosubstitution product might be less reactive:
o Electronic reasons. If the “E group” that added is electron withdrawing, it will
make the product aromatic ring less electron rich and subsequently less reactive
toward subsequent electrophilic addition.
o Steric reasons. Replacement of a small H with a larger “E group” will make the
monosubstitution product more crowded, which may interfere with subsequent
addition of additional electrophiles.
ZZ
E
acid
E-X
H
H
H
H
H
H-X +
ZZ
E
E
meta ortho para
monosubstitution products
++++etc.
Z Z
EEEE
E
double
substitution
triple
substitition
polysubstitution products
2. Position of Substitution: Ortho, Meta, or Para To a Pre-existing Substituent?
• Even if a reaction can be disciplined such that monosubstitution occurs to the
exclusion of double or triple substitution, what happens when substitution occurs on a
benzene that already has a substituent attached (Z ≠ H)? Will ortho, meta, and para
hydrogens be substituted with equal ease, so that a statistical mixture of ortho-, meta-,
and para-disubstituted products form? Or will substitution be selective? Somewhat
selective substitution is ordinarily possible based on two reasons:
o Electronic reasons. Rate-determining addition of E+ occurs with differing speeds
because of the electronic impact of Z on the delocalized cationic charge. If Z is
an electron donor, it will stabilize positive charge and facilitate ortho and para
addition relative to meta addition. If Z is an electron withdrawer, it will
destabilize positive charge and deactivate ortho and para addition relative to meta
addition.
o Steric reasons. Depending on the size of both Z and E, they will interact to
varying degrees in the pathway leading to the ortho product. Thus the ortho
product is normally destabilized for steric reasons relative to either the meta or the
para products.
