11/30/2012
Nitration of Aromatics
CH3
CH3
O2 N
NO2
dynamite (Acme)
toluene
NO2
tri-nitrotoluene (TNT)
?
Nitration of Methyl Benzoate
A Study of Electrophilic
Aromatic Substitution
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Nitration of Methyl Benzoate
CO2CH3
CO2CH3
HNO3, H2SO4
NO2
Nitration can introduce a nitro group into
three different positions on the aromatic
ring.
Mechanism of EAS
1) Formation of Reactive Electrophile
• Differs for each substituent being added
• Electrophile for nitration is +NO2
2) Reaction of Electrophile with Aromatic
Ring
3) Deprotonation to Regenerate Aromatic
Ring
Steps 2) and 3) are essentially identical for
all EAS reactions.
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Steps in EAS
H
H
E+
E
Deprotonation by a base at the tetrahedral
The reaction of the reactive electrophile
carbon containing the electrophile results
with the aromatic ring gives a high energy
in reformation of a stabilized aromatic ring
carbocation intermediate. This carbocation
with a new substituent (E) present.
is stabilized by resonance, but the aromatic
stabilization has been lost.
Steps in EAS
H
H
E+
E
E
Y
H
+
H-Y
Y
H
E
Product resulting from simple addition of
E+ and Y - does not occur because the
addition product is not aromatic.
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Nitration via NO2+
The reactive electrophile in nitration is NO2+
OH
O
N
O
H
OSO3H
OH2
O
O
N
N
O
O
+
H2O
In the first step, nitric acid acts as a base and
is protonated by the stronger sulfuric acid.
Then loss of water gives the nitronium ion,
NO2+
Nitration of Benzene
first step is the
reaction
of the by
The carbocation
is then
deprotonated
electrophilic
nitronium
with the
water,
the strongest
baseion
present
in the
nucleophilic
pi electrons
in the aromatic
sulfuric
acid/nitric
acid mixture.
ring to form a high-energy carbocation.
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EAS with Substituted Benzenes
Substituents can cause a compound to be either
more or less reactive than benzene
Substituents affect the orientation of the reaction
– the site of attack is affected
EAS with Substituted Benzenes
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Positional Selectivity
Y
Y
E+
Y
Y
E
E
ortho-product
meta-product
E
p ara-product
Three positional isomers are possible, but
they are never formed in equal amounts
The properties of the substituent Y controls
the selectivity.
Positional Selectivity
All electron-donating (activating) groups
give predominantly the ortho- and paraisomers as products (see red subst. above)
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Positional Selectivity
All strongly electron-withdrawing
(deactivating) groups give predominantly the
meta- isomer as product (see blue subst. above)
Positional Selectivity
The weakly deactivating halogens give
predominantly the ortho- and para- isomers as
product (see green subst. above)
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Activating ortho/para directors
The electron donation of activating groups is
greatest for the ortho- and para- intermediates
(and transition states).
Deactivating meta directors
The electron withdrawal of deactivating groups
is greatest for the ortho- and paraintermediates (and transition states), thus
making the meta pathway lowest energy.
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Halogens
The inductive effect of the electronegative halogens
leads to reduced reactivity, but the lone pairs on the
halogen still make the ortho and para pathways
faster than the meta pathway.
Methyl Benzoate
O
OCH3
C

O

OCH3
C 
Is the –CO2Me group an activating or
deactivating group?
Which product(s) do we expect to
predominate?
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Procedure suggestions
Sulfuric acid will be the solvent for the
methyl benzoate. Cool it in the ice bath
before adding the methyl benzoate.
The methyl benzoate is in dropper bottles.
Weigh out about 3.4 g and add to the cooled
sulfuric acid.
Do NOT add the nitrating acid mixture all at
once! Add drop wise over about a three
minute period.
Procedure suggestions (Cont.)
You need to have the ice melted before you
filter to isolate your crystalline product.
Develop your TLC plate to near the top (less
than 10 mm) of the plate; you need to
distinguish between the isomeric products.
“Mother liquor” is the solvent (filtrate) that
passed through the filter in isolating the
recrystallized product – should contain more
impurities and minor products.
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Safety
Be extremely careful with the strong acids used
in this experiment. They will rapidly burn skin!
Be careful with the autodispensers in the hood.
Do not touch the tips with hands or arms. Be
careful not to dispense too rapidly. Wipe up all
spills outside the dispensing tray.
Use safety showers immediately for any spill of
acid on clothing. Two students of same gender
should bring fire blanket to shower to act as
modesty curtain; other students should leave lab.
Safety
Avoid contact with the organic products in this
reaction. They are strong irritants.
Clamp your recrystallization flask in the ice bath
or it will overturn. Clamp your filter flask!
Read the safety box in the lab manual at the end of
the experimental section for this experiment again
before starting this experiment.
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Clean-up Procedures
Wipe all spills of acids with a wet paper towel
and then with bicarbonate solution.
Wipe your bench area with a moist paper
towel before you leave the lab.
There are TWO waste bottles – one for
organic waste and one for aqueous waste
(don’t mix!).
TLC plates and filter paper also go into
waste containers.
Univ. of Maryland Organic II Lab
Explosion – Sept. 26, 2011
Waste Container
hood after explosion
and fire when 2
students poured
nitrating acid into
organic waste
container!!!
• ALWAYS pour waste into the appropriate container.
• You will not have waste nitrating acid in today’s lab because
you will be given EXACTLY the correct amount from an
autodispenser!
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