Chemistry 351 at Winona State University – Professor Thomas Nalli
Experiment #7. Electrophilic Aromatic Substitution
You will be assigned an electrophilic substitution reaction to carry out. Crude product
mixtures will be analyzed by 1H NMR and GC/MS. The crude products will then be
purified by recrystallization (procedures will be provided later in a separate handout) and
once again analyzed by 1H NMR and GC/MS. The goal is to determine o:m:p ratios
formed in the reactions (i.e., what is the directing effect of the substituent).
1. Nitration of bromobenzene
2. Nitration of iodobenzene
3. Nitration of methyl benzoate
4. Butylation of phenol
5. Butylation of tert-butylbenzene
Reaction Procedures
General. Run the reaction using the apparatus indicated in each procedure. Begin by
placing the stir bar in the r.b. flask and clamping the flask to the ring stand.
Nitration of bromobenzene/iodobenzene. Add 4.0 mL of HNO3(conc) and 4.0 mL of
H2SO4(conc) to the reaction flask. Now assemble the rest of the apparatus shown in
Figure 1, cooling the mixture with stirring on a cold water bath to approx 30ºC. Add 4.5
mL of the assigned halobenzene (iodobenzene or brombenzene) or in small portions
(~0.5 mL) through the top of the condenser to the stirring solution. The rate of addition
should be adjusted so that the temperature does not exceed 55ºC. After all of the
bromobenzene has been added and the temperature has begun to decrease gently heat the
solution using a hot water bath for 15 minutes (keep the temperature below 60ºC). After
cooling to room temperature pour the mixture into 40 mL of crushed ice in a beaker.
After the ice has melted, carry out vacuum filtration with a Buchner funnel to isolate the
precipitate crude product mixture. Wash the filter cake thoroughly with cold distilled
water until the filtrate is no longer acidic as indicated by pHydrion paper. Recrystallize
the product from 95% ethanol. Safety: Nitric acid and sulfuric acid are extremely
corrosive and cause severe burns. Wear gloves and rinse any skin exposure
immediately with lots of water. Do not dispose of excess of either of the acids down
the drain.
Nitration of methyl benzoate. Add 6.0 mL of H2SO4(conc) to the reaction flask, cool to
3-4 ºC on an ice bath, and then add 5.5 mL of methyl benzoate. Now assemble the rest of
the apparatus shown in Figure 1, cooling the mixture with stirring on an ice bath to at
least 10ºC. While this solution is cooling and the apparatus is being assembled, one team
member should prepare a mixture of 4 mL HNO3(conc) and 4 mL H2SO4(conc) in a small
Erlenmeyer flask and cool it on ice. The cooled nitric acid/sulfuric acid solution is then
added dropwise to the cooled and stirring methyl benzoate solution. (Use a Pasteur pipet
to add the solution drop by drop through the top of the condenser.) The rate of addition
should be adjusted so that the temperature does not exceed 15ºC. After the addition is
complete allow the mixture to warm to room temperature, let stand for 15 min and then
pour it into 50 mL of crushed ice in a beaker. After the ice has melted, carry out vacuum
filtration with a Buchner funnel to isolate the precipitate crude product mixture. Wash the
filter cake thoroughly with cold distilled water until the filtrate is no longer acidic as
indicated by pHydrion paper. Finally, wash with two 5-mL portions of cold methanol.
Recrystallize the product from methanol. Safety: Nitric acid and sulfuric acid are
extremely corrosive and cause severe burns. Wear gloves and rinse any skin
exposure immediately with lots of water. Do not dispose of excess of either of the
acids down the drain.
Butylation of phenol. Run this reaction in a fume hood. Add 6.5 mL of tert-butyl
chloride to the reaction flask and then add 4.7 g of phenol. Assemble the rest of the
apparatus shown in Figure 1, stirring the mixture so that the phenol eventually dissolves
before going on. In the meantime, weigh 0.5 g of AlCl3 into a dry screw-cap vial and
immediately cap the vial. Remove the thermometer and thermometer adapter and add 0.5
g AlCl3 a little at a time to the stirring solution. HCl gas evolution should begin
immediately. Replace the thermometer and monitor the temperature. If it begins to warm
up much (above 30-35ºC) then cool briefly on a cold water bath. Allow 20-30 min for the
reaction to go to completion. Add 25 mL water and break up the solid that forms with a
spatula as much as you can. Carry out vacuum filtration with a Buchner funnel to isolate
the crude product mixture. Wash with a few mL of cold water. Store the crude solid in
your drawer until next week. Recrystallize the product from petroleum ether (bp 6090ºC). Safety: phenol is corrosive to the eyes and skin and may cause dermatitis.
Wear gloves and rinse any skin exposure immediately with lots of water. Aluminum
chloride dust is extremely hygroscopic and reacts rapidly with water, even the
moisture on your hands, producing fumes of HCl. Do not allow AlCl3 to come in
contact with your skin. If it does rinse the affected area with lots of water. This
reaction evolves HCl gas, therefore it is essential that it be run in a functioning fume
hood.
Butylation of tert-butylbenzene. Run this reaction in a fume hood. Add 6.5 mL of tertbutyl chloride to the reaction flask and then add 7.7 mL of tert-butylbenzene. Now
assemble the rest of the apparatus shown in Figure 1, cooling the mixture with stirring on
an ice bath to at least 3ºC. In the meantime, weigh 0.5 g of AlCl3 into a dry screw-cap
vial and immediately cap the vial. Remove the thermometer and thermometer adapter and
add approximately ¼ of the AlCl3 to the stirring cold solution. HCl gas evolution should
begin immediately. Replace the thermometer and monitor the temperature. When it has
once again cooled to near 3º add a second ¼ of the AlCl3. Continue like this until all of
the catalyst has been added. When a solid begins to form remove the reaction from the
ice bath and let stand for 5 min. Add 25 mL water and then pour the contents into approx
15 mL of crushed ice. After the ice has melted, carry out vacuum filtration with a
Buchner funnel to isolate the crude product mixture. Wash the filer cake with cold water.
Store the crude solid in your drawer until next week. Recrystallize the product from
methanol. Safety: Aluminum chloride dust is extremely hygroscopic and reacts
rapidly with water, even the moisture on your hands, producing fumes of HCl. Do
not allow AlCl3 to come in contact with your skin. If it does rinse the affected area
with lots of water. This reaction evolves HCl gas, therefore it is essential that it be
run in a functioning fume hood.
Figure 1. Reaction apparatus which allows temperature monitoring.
Figure 2. Reaction apparatus which facilitates dropwise addition.