Friedel-Crafts Acylation of Ferrocene
Friedel-Crafts reactions are examples of electrophilic aromatic substitution reactions. The
reaction involves the substitution of hydrogen on the aromatic ring system by an electrophilic
carbon species forming a new carbon-carbon bond. Friedel-Crafts reactions may be used to
introduce either an alkyl or acyl group.
Ferrocene does not undergo addition reactions typical of cyclopentadiene, but undergoes
electrophilic aromatic substitution. The Friedel-Crafts acylation reaction of ferrocene involves
the addition of the acylium cation to one of the carbon atoms on the ring, followed by loss of a
proton (to solvent). The acylium cation is produced from acetic anhydride, which also serves as a
solvent for this reaction. If only one ring reacts, then the product is the orange acetylferrocene. If
both rings react, then the product is the red 1,1-diacetylferrocene. The reaction time of this
experiment is reduced to limit the formation of 1,1-diacetylferrocene.
Your objectives in this experiment will be to synthesize, isolate, and characterize acetylferrocene.
The reaction equation is shown below. In this experiment you will also become familiar with a
technique called column chromatography, which can be used to separate the desired product
from unreacted starting material and side products. The compounds are colored which will make
it easy to see the separation. Melting temperature analysis will be used to characterize the
synthesized product.
O
O
Fe
+
Ferrocene
H3C
CH3
O
O
H3PO4 (aq)
CH3
Acetic anhydride

Fe
O
+
Acetylferrocene
H3C
OH
Acetic acid
OBJECTIVES
In this experiment, you will
 Synthesize acetylferrocene.
 Isolate and purify the product using column chromatography.
 Measure the melting temperature range of your product.
Organic Chemistry with Vernier
© Vernier Software & Technology
1
MATERIALS
Part I Synthesis Materials
50 mL round bottom flask
stir bar
drying tube
ring stand with utility clamp
Büchner funnel
filtering flask
filter paper
10 mL graduated cylinder
spatula
cotton plug
Drierite®
cork ring
100 mL beaker
two 250 mL beakers
disposable Pasteur pipets and bulb
ferrocene
85% phosphoric acid solution
liquid acetic anhydride
distilled water
ice
sodium bicarbonate, NaHCO3, solid
grease
balance
weighing paper
watch glass
magnetic stirrer/hot plate
Temperature Probe or thermometer
compressed air
pH paper (optional)
Part II Column Chromatography
10 mL disposable serological pipet, glass
cotton plug
sand
silica gel
weighing paper
disposable Pasteur pipets and bulb
four 250 mL Erlenmeyer flasks
400 mL beaker
10 mL graduated cylinder
50 mL graduated cylinder (optional)
hexane
acetone
diethyl ether
9:1 hexane/acetone mixture
two 20150 mm test tubes
test tube rack
hot plate
Temperature Probe or thermometer
boiling stone
compressed air
Part III Melting Temperature
LabQuest or computer interface
LabQuest App or Logger Pro
Vernier Melt Station
glass capillary tubes, one end closed
tissues (preferably lint-free)
samples from Part II
mortar and pestle
PROCEDURE
Part I Synthesis
1. Obtain and wear goggles. Protect your arms and hands by wearing a long-sleeve lab coat and
gloves. Conduct this reaction in a fume hood.
2. Prepare the reaction mixture. CAUTION: Handle the phosphoric acid and acetic anhydride
with care. Both substances can cause painful burns if they come in contact with the skin.
a. Weigh out 1.0 g of acetic anhydride in the 50 mL round bottom flask and record to the
nearest 0.01 g.
b. Weigh out about 0.25 g of ferrocene and transfer to the round bottom flask. Record the
mass to the nearest 0.01 g.
2
Organic Chemistry with Vernier
Friedel-Crafts Acylation of Ferrocene
c. Add a stir bar to the flask.
d. Clamp the round bottom flask securely to the ring stand, lower onto the stir plate, and
begin stirring.
e. Slowly add 8 drops of 85% phosphoric acid to the mixture over 2 minutes. This reaction is
exothermic.
3. After the addition of the phosphoric acid, equip the flask with a drying tube containing
Drierite®. Grease the joints to prevent the glass from sticking.
4. Prepare a 65°C hot water bath using a 250 mL beaker. Monitor the temperature using a
Temperature Probe or thermometer.
5. Heat the solution in the hot water bath for 10 minutes while stirring the reaction.
6. Fill half of a 100 mL beaker with ice. Pour the solution over the ice. Rinse the round bottom
flask with a small amount (1–2 mL) of cold distilled water.
7. Add small pea size amounts of solid sodium bicarbonate to the solution until the gas
evolution stops. The pH may be tested with pH paper to determine neutrality.
Note: Minimize adding excess NaHCO3.
8. Prepare an ice water bath in a 250 mL beaker and cool the resulting orange solution for
30 minutes.
9. Collect the solid.
a.
b.
c.
d.
Weigh the filter paper and record the mass to the nearest 0.01 g.
Set up a vacuum filtration with the Büchner funnel.
Collect the orange precipitate by vacuum filtration.
Wash the solid with cold distilled water to remove impurities until it is a pale orange
color. Note: Use a minimal amount of water because the product is slightly soluble in
water.
e. Transfer the filter paper with the crude solid onto a clean watch glass to air dry. Direct a
gentle stream of air (low flow) to help dry the solid.
f. When dry, weigh the product and record the mass to the nearest 0.01 g.
Part II Column Chromatography
10. In a test tube, dissolve approximately 0.1 g of your sample in 0.5 mL of diethyl ether.
11. Prepare the elution solvent mixture.
a. Obtain 50 mL of hexane in an Erlenmeyer flask.
b. Obtain 10 mL of acetone in another Erlenmeyer flask.
c. Prepare 30 mL of 9:1 hexane/acetone mixture in an Erlenmeyer flask by mixing 27 mL of
hexane and 3 mL of acetone.
Organic Chemistry with Vernier
3
12. Assemble the chromatography column. CAUTION: Silica powder is harmful if inhaled. Use
only in the fume hood.
a. Place a small piece of cotton into the bottom of the 10 mL serological pipet followed by
0.5 cm of sand and enough silica to fill the pipet about 2/3 full. Note: Weighing paper
may be used to help fill the pipet with silica.
b. Gently tap the tip of the pipet on the table top for 1–2 minutes to pack the silica.
c. Add another 0.5 cm of sand to the top of the pipet.
13. Obtain two test tubes to collect the column fractions and a 250 mL Erlenmeyer flask for
waste. Important: Once you start the elution process, it cannot be stopped. You must go to
completion. Read Steps 14–16 carefully before continuing.
14. Prepare the column for chromatography.
a. Place the waste flask under the pipet column and elute approximately 10 mL of hexane
through the column. Note: If air bubbles or cracks appear in the column, discard and
repeat Step 12. Use compressed air at very low pressure to push the solvent through.
b. Elute another 5 mL of hexane. Important: Do not let the column get dry during this
procedure. Replenish with solvent as needed.
c. Once the solvent has drained to just above the silica, pipet your sample evenly onto the
column.
d. Allow the solution to adsorb onto the silica making sure the solvent layer does not drop
below the silica layer.
e. Add 1 mL of hexane down the sides of the column and drain until the solvent level is
below the top of the sand. Repeat this procedure until your compound is a tight band
bound on the silica.
15. Carefully fill the pipet column with 9:1 hexane/acetone. Add solvent as needed during the
procedure.
16. Collect the fractions during the elution process. Note: To slow down the flow rate, remove
the air pressure.
a. Collect the clear portion in the waste flask.
b. Collect the ferrocene in a clean test tube.
c. After all the ferrocene has passed through the pipet column, continue adding
9:1 hexane/acetone.
d. Collect the acetylferrocene fraction in a clean test tube.
e. Once the acetylferrocene fraction has been collected, collect the remaining solvent in the
waste flask.
17. Prepare a 70°C hot water bath in a 400 mL beaker. Monitor the temperature using a
Temperature Probe or thermometer.
18. Place a boiling stone in each of the test tubes and carefully evaporate the solvent using the
hot water bath.
19. Collect the dry solid for melting temperature analysis.
4
Organic Chemistry with Vernier
Friedel-Crafts Acylation of Ferrocene
Part III Test the Melting Temperature of Ferrocene and Acetylferrocene.
20. Obtain a small amount of ferrocene from Part II. The solid should be in a powdered form. If it
is not, use a mortar and pestle to carefully grind the solid to a powder.
21. Prepare a sample for melting.
a. Pack a capillary tube 3–4 mm (~1/8 inch) deep with your sample by inserting the open end
into a small pile of the solid. A small amount of the solid will be pushed up into the tube.
b. Tap the closed end of the capillary tube on the table top to compress the sample into the
closed end.
c. Check the control knob on the Melt Station to confirm that it is in the Off position.
d. Carefully insert the capillary tube of solid into one of the sample holders of the Melt
Station.
22. Connect the Melt Station power supply to a powered electrical outlet.
23. Connect the Melt Station sensor cable to LabQuest or to a computer interface.
24. Start the data-collection program, then choose New from the File menu. You are now set up
to take melting temperature data for up to 20 minutes.
25. In the first trial, you will want to observe the melting process and make a rough estimate of
the melting temperature of your sample. Don’t worry if the heating rate is a bit too rapid, and
the sample melts too quickly. To do this:
a. Start data collection.
b. On the Melt Station, turn the control knob to a setting of 180ºC. The red light will turn on
indicating active heating.
c. Carefully observe your sample. If the solid begins to melt, click Mark to mark the
temperature on your graph (or press the D key on the computer or the OK button on
LabQuest). When the entire solid has completely melted, click Mark again. The two
values marked on your graph describe the estimated melting temperature range of your
substance.
d. If the solid does not melt by the time the temperature gets to 150ºC, turn the control knob
to the 220ºC setting. Continue observing your sample, and if the sample begins to melt,
mark the temperatures on the graph as previously described.
e. If the sample has not melted by the time the temperature gets to 190ºC, turn the knob to
the Rapid Heat setting. When the sample finally begins to melt, mark the graph as
previously indicated.
f. When you have determined the approximate melting temperature range for the sample,
stop data collection. Store the run by tapping the File Cabinet icon in LabQuest, or
choosing Store Latest Run from the Experiment menu in Logger Pro. Discard the capillary
tube and sample as directed by your instructor.
g. On the Melt Station, turn the control knob to the Fan/Cooling setting to get ready for the
next trial. The blue light will turn on indicating that the fan is cooling the Melt Station.
26. Now that you have a rough idea of the melting temperature, a more accurate determination of
the melting temperature can be made. Use a previously prepared sample in a capillary tube, as
described in Steps 2021, to determine the melting temperature of the sample:
a. Start data collection.
b. On the Melt Station, turn the control knob to the Rapid Heat setting.
Organic Chemistry with Vernier
5
c. Carefully observe the temperature vs. time graph. When the temperature is within
approximately 10ºC of the lowest possible melting temperature of your sample, turn the
control knob to a temperature setting corresponding to your expected melting temperature.
d. Carefully observe your sample. When the solid begins to melt, click Mark to mark the
temperature on your graph. When the entire solid has completely melted, click Mark
again. The two values marked on your graph describe the estimated melting temperature
range of your substance. When you are finished with this step, stop data collection.
e. Store the run.
f. Discard the capillary tube and sample as directed by your instructor.
g. On the Melt Station, turn the control knob to the Fan/Cooling setting to get ready for the
next trial.
27. Repeat Step 26 until you have determined the melting temperature range of the solid. Record
the range in the data table.
28. Prepare an acetylferrocene sample for analysis according to Steps 20–21.
29. Repeat Step 25–27 for the acetylferrocene sample.
30. At the end of the experiment, turn the control knob on the Melt Station to Off.
DATA TABLE
Part I Synthesis of Acetylferrocene
Mass of ferrocene (g)
Mass of acetic anhydride (g)
Mass of filter paper (g)
Mass of filter paper and product (g)
Mass of product (g)
Part III Melting Temperature
Measure melting temperature
range (°C)
Isolated ferrocene
Isolated acetylferrocene
DATA ANALYSIS
1. What is the theoretical yield of acetylferrocene in your synthesis if the reaction went to
completion? What is the actual yield?
6
Organic Chemistry with Vernier
Friedel-Crafts Acylation of Ferrocene
INSTRUCTOR INFORMATION
1. This experiment can be divided into two days. The synthesis and chromatography are
completed on the first day. The melting temperature analysis is completed on the second day.
2. Assemble the drying tube by placing a small piece of glass wool or cotton near the tip, fill
with Drierite®, and cover with a second piece of glass wool or cotton.
3. Prepare cold distilled water by placing wash bottles with distilled water in an ice water bath.
4. It is important to use a small amount of cold distilled water to wash the product. The product
is somewhat soluble in water and excess water may result in a lower yield.
5. When preparing the column, the silica gel should be handled in the fume hood.
6. The column is packed using the dry-pack method.
7. Once the elution process is started, it cannot be stopped. Remind the students the importance
of reading through Steps 14–16 before adding solvent to the column.
8. Compressed air at a low pressure is used to flash the solvent through the column to accelerate
the procedure. If compressed air is unavailable, a pipet bulb can be used to push the solvent
through the column. Using a pipet bulb will create a slight vacuum. Be careful when
removing the pipet bulb from the column so that the silica is not pulled into the bulb.
9. The melting temperature range of the compounds is listed below.
Compound
ferrocene
acetylferrocene
Melting temperature range
(°C)
172–174
81–83
10. Dispose of waste properly.
HAZARD ALERTS
Acetic anhydride: Strongly irritating and corrosive. Moderate fire risk (flash point 49°C). Causes
severe eye damage. Wear eye protection. Have access to eyewash. Vapors are strongly irritating.
Open and dispense in fume hood. Reacts (sometimes delayed) violently with water. Moderately
toxic by ingestion and inhalation. HMIS Classification: Health hazard3, Flammability2,
Physical hazard2.
Phosphoric acid (o-phosphoric acid): Skin and eye irritant. Toxic by ingestion and inhalation.
Burns tissue. HMIS Classification: Health hazard3, Flammability0, Physical hazard0.
Ferrocene: Harmful if ingested. May cause respiratory tract irritation. Eye and skin irritant.
Moderately toxic by inhalation. HMIS Classification: Health hazard1, Flammability0, Physical
hazard3.
Organic Chemistry with Vernier
7
Sodium bicarbonate: May be harmful by ingestion or inhalation. May cause eye and skin
irritation. HMIS Classification: Health hazard1, Flammability0, Physical hazard0.
Hexanes: Serious fire hazard (flash point 23°C). Severe eye and skin irritant. Moderately toxic
by ingestion. Vapor causes weakness, fatigue, nausea and headache. HMIS Classification: Health
hazard2, Flammability3, Physical hazard0.
Acetone: Fire hazard (flash point 17.0°C). Store in dedicated flammables cabinet. Moderately
toxic by inhalation or ingestion. Moderately toxic by ingestion. Vapor causes weakness, fatigue,
nausea and headache. Skin and eye irritant. HMIS Classification: Health hazard2,
Flammability3, Physical hazard0.
Diethyl ether: Serious fire hazard (flash point40.0°C). Irritating to body tissues. Moderately
toxic by ingestion. Vapor causes weakness, fatigue, nausea and headache. Skin and eye irritant.
HMIS Classification: Health hazard2, Flammability4, Physical hazard2.
Silica: Moderately toxic by inhalation and ingestion. May cause skin and eye irritation. HMIS
Classification: Health hazard1, Flammability0, Physical hazard0.
Drierite®: May be harmful if inhaled. May cause respiratory tract irritation. May cause skin and
eye irritation. Toxic if swallowed. HMIS Classification: Health hazard2, Flammability0,
Physical hazard0.
The hazard information reference is: Sigma-Aldrich Co.,
1-800-325-3010, www.sigmaaldrich.com/safety-center/msds-search.html.
COMPOUND INFORMATION
8
Compound
Chemical formula
Melting temperature range
(C)
Molar mass
(g/mol)
ferrocene
C10H10Fe
172–174
186.03
sodium bicarbonate
NaHCO3
300
84.01
silica
SiO2
>1600
60.08
Organic Chemistry with Vernier
Friedel-Crafts Acylation of Ferrocene
Compound
Chemical formula
Boiling temperature
range (C)
Molar mass
(g/mol)
Density
(g/mL) at 25°C
hexane
(mixture of isomers)
C6H14
68–70
86.18
0.672
acetone
C3H6O
56
58.08
0.791
diethyl ether
C4H10O
34.6
74.11
0.706
acetic anhydride
C4H6O3
138–140
102.09
1.08
phosphoric acid
(85%)
H3PO4 in H2O
158
98.00
1.685
SAMPLE RESULTS
Melting temperature graph of acetylferrocene
Melting temperature graph of ferrocene
Organic Chemistry with Vernier
9