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Electrophilic Aromatic
Substitution
PURPOSE OF THE EXPERIMENT: Demonstrate the regioselectivity of electrophilic
aromatic substitution reactions for monosubstituted aromatic compounds.
BACKGROUND REQUIRED: You should be familiar with vacuum filtration, melting point
measurement, and recrystallization techniques.
BACKGROUND INFORMATION: Most substitution reactions at aliphatic carbon atoms are
nucleophilic. However, aromatic substitution reactions are generally electrophilic,
due to the high electron density of the benzene ring. The species reacting with the aromatic ring
is usually a positive ion or the positive end of a dipole. This electron-deficient species, or
electrophile, may be produced in various ways, but the reaction between the electrophile and the
aromatic ring is essentially the same in all cases. The most common electrophilic aromatic
substitution mechanism is the sigma complex mechanism, shown in Figure 1.
Step 1:
CH
E
+
HC
E
H
E
+
CH
Step 2:
+
CH
H
BE
HB
Figure 1: Electrophilic substitution at an aromatic ring occurs by formation of a sigma complex (step 1)
and subsequent loss of a proton to a base (step 2). Note that the intermediate is NOT aromatic, but the
product is.
In the first step of the reaction, benzene donates an electron pair to the electrophilic species,
designated E+. A carbocation intermediate is formed, called an arenium ion or sigma complex.
These sigma complexes can he written in three resonance forms. Although the sigma complex is
stabilized by these resonance forms, it is destabilized by the loss of aromatic stability (about 36
kcal/mol). This aromatic stability is regained in the second step of the reaction, consisting of
elimination of a proton from the sigma complex, forming a substituted benzene ring (and
thereby reforming an aromatic system).
Z
H
H
E
Figure 2: When the electrophile attaches at a position ortho- or para- to the substituent, there will be a
resonance form with the carbocation at the substituted carbon. This will not occur when the electrophile
attaches in the meta- position.
+ 2 H2SO4
In this experiment, you will nitrate acetanilide as the substrate. You will use melting point data
to determine which regioisomer is formed. (You should be able to predict the most likely
product ahead of time!). The reaction, without showing regiochemistry, is:
O
H3C
NH
H3C
NH
NO
2
quantity
molar mass
mp
acetanilide
ethanol, 95%
0.5 g
510 mL
135.17
46.07
113115
nitroacetanilide
nitric acid conc.
sulfuric acid conc.
1.0 mL 63.01
1.2 mL 98.08
bp
78
180.16
Preview
PROCEDURE
Chemical Alert
acetanilide toxic and irritant
ethanol flammable and irritant
nitroacetanilide irritant
concentrated nitric acid toxic and oxidizer
concentrated sulfuric acid toxic and oxidizer
Caution: Wear departmentally approved safety goggles at all times while in the chemistry
laboratory.
1. Preparing the Ice-Water Bath and Chilled Water
Place approximately equal volumes of ice and tap water into a 400-mL beaker, so that the
beaker is 75% full. Prepare chilled water for Parts 3 and 4 by pouring approximately 30 mL of
distilled or deionized water into a 125-mL Erlenmeyer flask and placing the flask into the icewater bath.
2. Preparing the Nitrating Solution
Caution: Nitric acid and sulfuric acid are toxic and oxidizing. The mixture you are preparing
can cause severe burns. Prevent eye, skin, clothing, and combustible material contact. Avoid
inhaling vapors and ingesting these compounds. I would recommend using gloves for this
procedure.
Label two test tubes nitric acid and sulfuric acid, respectively. Transfer 1.0 mL of
concentrated nitric acid into the nitric acid tube. Transfer 1.2 mL of concentrated sulfuric acid
into the sulfuric acid tube. Chill both test tubes containing the acids in the ice-water bath for
at least 5 min.
Caution! Caution! Caution!: Mixing concentrated sulfuric and nitric acids is a highly
exothermic reaction. Hot acid mixtures can rapidly reach their boiling points; this may
result in spattering and cause acid burns. Make certain the acids are cold before mixing;
also, that the mixture remains cold during the mixing process.
Use an eyedropper or Pasteur pipette to very slowly add the cold sulfuric acid dropwise to the
cold nitric acid. Swirl the reaction mixture after every 3 drops. After adding all the sulfuric acid,
allow the nitrating solution to stand in the ice-water bath for 10 min so it can fully cool. You
can go on to step 3 while it is cooling.
3. Nitrating the Aromatic Compound
Caution: Acetanilide is toxic and an irritant. Nitroacetanilide (the product) is an irritant.
Prevent eye, skin, and clothing contact. Avoid inhaling dust and ingesting these compounds.
Place 0.50 g of acetanilide into a 25-mL Erlenmeyer flask. Add 1.0 mL of concentrated sulfuric
acid. The acetanilide should dissolve after a few minutes, but if a small amount remains, you
can proceed because it will dissolve as you add the nitrating solution in the next step.
Clamp the flask containing the mixture to a ring stand. Lower the flask into the ice-water bath,
and let it cool for 3 min. Take care to prevent bath water from entering the reaction flask, which
will slow the reaction down and significantly lower your yield! Use an eyedropper or Pasteur
pipette to slowly add the nitrating solution in the test tube to the Erlenmeyer flask containing the
acetanilide and sulfuric acid; the flask should remain in the ice bath during this entire process.
NOTE: Rapid addition of the nitrating solution will cause the reaction mixture to heat up,
turning the mixture dark brown. This dark brown product is difficult to recrystallize and will
affect the melting point! It is normal for the solution to turn amber or yellowish as the ring is
nitrated, because the product is a pale yellow compound. But it should NOT turn dark brown
(like a coffee color, for instance).
After adding all the nitrating solution, allow the mixture to stand in the ice-water bath for
30 minutes, swirling the flask about every 5 minutes. After 30 min, add 10 mL of chilled
deionized or distilled water to a 50-mL beaker. Slowly and carefully add the cold reaction
mixture, with stirring, to the chilled water. Allow the chilled solution to stand for 5-10 minutes
to complete crystal formation. The product is a off-white or pale yellow crystalline solid.
4. Isolating, Purifying, and Characterizing the Product
Caution: Ethanol is flammable and irritating. Keep away from flames and other heat sources.
Avoid inhaling vapors and ingesting this compound.
Filter the reaction mixture using vacuum filtration. You can use deionized water to rinse the
crystals out of the small Erlenmeyer flask. Wash the crystals with 10 mL of chilled water to
remove any residual acid. Allow your product to air dry in the filter funnel for 10 min.
Your instructor may wish you to recrystallize your product from 95% ethanol check with your
instructor to see if this is necessary before beginning the procedure! The recrystallization
should require about 10 mL of hot ethanol. Filter the crystals using vacuum filtration. Allow
your product to air dry in the filter funnel for 10 minutes.
Because the product is being isolated from water (which is difficult to quickly remove from
your product), the weight and mass will be recorded the week following the experiment.
After drying the product for at least one week, weigh your product and record its mass.
Measure the melting point of your product. [You should be familiar with the procedure of
measuring melting point from Organic I lab, but you instructor can assist you with this if you
are unsure]. If the melting point of your product exceeds the operating range of the
thermometer, record the melting point as < 150C .
5. Cleaning Up
There is no waste container for this experiment. The filtrate is acidic but non-toxic; wash it
down the sink, making sure to dilute it by running water afterwards.
Place your recovered product in a beaker, label it with your name, and give it to your instructor
for next week. Clean your glassware with soap or detergent.
Caution: Wash your hands thoroughly with soap or detergent before leaving the laboratory.
_____________________ grams
_____________________ grams
Mass of acetanilide:
_____________________ grams
_____________________ grams
_____________________ grams
Mass of product:
_____________________ grams
_____________________ C
4a. Below you will find C-NMR, H-NMR and IR spectra for the reactant in today's lab acetanilide. (Note that on the H-NMR spectrum for acetanilide, there are TWO signals
in the range 7 - 8 ppm).
On the following page, you will find the corresponding spectra for the major
product, a nitrated form of acetanilide.
Provide a detailed analysis of each spectrum, with particular emphasis on the
contrasting features of the reactant and product. For the 1H-NMR spectrum, the best
way to do this is to draw the structure of the compound, label each hydrogen type with a
letter, and label the corresponding peaks in the spectrum with the same letter (as with
many examples in class and in the book). You can do the same thing for the 13C-NMR
spectrum, but labeling the carbons instead.
4b.
Is there anyway to determine from the spectral data whether the product is
ortho-, para-, or meta-substituted? What indications are there?
Acetanilide:
Pre-Laboratory Assignment
Name ___________________________________________________________________
1. What precautions must be taken when using concentrated acids?
2.
(a) At what position(s) will electrophilic aromatic substitution occur for the following
compounds?
bromobenzene
toluene
nitrobenzene
phenol
benzoic acid
benzaldehyde
(b) In the list above, which compound is the most reactive? Briefly explain; in particular, why
is this compound more reactive than the other activated rings on the list?
(c) Which compound is the least reactive? Briefly explain; in particular, why is this compound
less reactive than the other deactivated rings on the list?
3. Calculate the theoretical yield (in grams) for the mononitration of acetanilide, assuming that
you begin with 0.50 g of acetanilide. Acetanilide is the limiting reactant. You must show your
work to receive credit on this question; use the back of the page if you need additional space.
(You may wish to make a copy of this result before submitting the pre-lab assignment; you will
be doing a similar calculation for one of the post-lab questions).
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