Experiment 6: Synthesis and Purification of Acetyl Ferrocene
Assigned Reading: procedure (below), lab text column chromatography (OP16, pp 616-624)
Time for Experiment: 2 lab periods
Prelab: Include in a notebook entry: reference for the experiment, balanced chemical reaction for the
preparation, a mechanism for the reaction, table of materials with relevant physical properties and
hazards (some of which are given below) along with the theoretical yield, and an outline of the
procedure to be followed.
hazards: acetic anhydride and phosphoric acid are strong corrosives; hexane, petroleum ether, and ether
are all extremely flammable
Procedure: (Taken in part from Macroscale and Microscale Organic Experiments by K. L. Williamson)
C H3
C H3
O
Fe
+
85% H3 PO4
Fe
O
O
+
CH3 CO2 H
O
C H3
ferrocene
bis(cyclopentadienyl)iron
mw 186.04, mp 172-4
acetic anhydride
mw 102.09
bp 139.5 ˚C, d 1.08 g/mL
acetylferrocene
mw 228.08,
mp 85-86 ˚C
acetic acid
mw 60.1
bp 118 ˚C, d 1.049
note: A hot water bath will serve as the heat source for this reaction. Before starting, prepare the large
beaker or dish of hot water on a heating plate or large sand bath.
(A) The Reaction: Friedel-Crafts Acylation of Ferrocene
Carefully add 2.0 mL of 85% phosphoric acid to 10 mL of acetic anhydride in a 25 mL roundbottomed flask and equip the flask with a reflux condenser and a calcium chloride drying tube.
Next add 3.0 g ferrocene in 2-3 increments with swirling and heating in a hot water bath (90-100
˚C) over a period of about 7-10 minutes. After all the ferrocene has been added, heat the mixture
in boiling water for an additional 10 minutes or until solution is deep purple/brown (a light orange
solution is under-reacted and a jet black solution is over-reacted). The mixture should turn dark.
Pour and scrape out the reaction mixture into 50 g (~100 mL) of crushed ice in a 400 mL beaker
and rinse the flask with 10 mL of water. Stir the aqueous mixture for a few minutes with a glass
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rod to generate a slurry, add 75 mL of 10% sodium hydroxide solution (the solution should still be
acidic) and then add solid sodium bicarbonate (careful - foaming) until the solution is pH neutral.
Stir and crush all lumps and allow the mixture to stand for 20 min and collect the crude product by
suction filtration. Press the crude material as dry as possible between sheets of filter paper. Once
the sample is mostly dry, weigh it to determine the crude yield and separate 250 mg of the material
to be purified by column chromatography in the next lab period (procedure given below). Of the
remaining sample, save a little (~10 mg for TLC and mp) and transfer the remainder to an
Erlenmeyer flask and add ~70 mL of hexane. Boil the solvent on your hot water bath (caution:
keep it in the hood, use a clamp, and use a boiling stick) for a few minutes and then decant the dark
orange solution into another Erlenmeyer flask, leaving behind any gummy residue of polymeric
material. Treat the resulting solution with decolorizing carbon and swirl and then gravity filter the
warm solution through fluted filter paper in a warm stemless funnel into a 100 mL beaker. Reduce
the volume to ~ 20 mL by evaporation (use boiling stick) and then allow the solution to cool
slowly to room temperature and then cool further in an ice bath to induce crystallization. Rosettes
of dark orange-red needles of acetylferrocene will form and may be collected by vacuum filtration
on a Buchner funnel. Wash the crystals with a small amount of cold hexane. Pure acetylferrocene
has mp 84-85 ˚C. Your yield should be about 1.5 g.
(B) Day 2 - Column Chromatography of 250 mg of crude acetylferrocene
Generally, before running a column separation of a mixture, one checks the composition of the mixture
by TLC and finds good conditions by TLC for the separation. In our case, it has been determined
already what conditions to use for the column chromatography. Nevertheless, please run a TLC analysis
of your crude material prior to running the column separation to get an idea about the composition of
your crude product. You can use a silica gel plate with elution by 2:1 ether:petroleum ether.
(i) Preparing the column: This task should take about 10-15 minutes. A well packed column is essential
to a successful chemical separation. Assemble the 3 part chromatography column provided (if
needed) and clamp it vertically using 2 clamps to hold it exactly straight. Insert a plug of glass
wool into the column and stuff it firmly against the stopcock with a long glass rod. Using a funnel,
deliver some clean sand onto the glass wool to the height of ~1 cm. Make sure the stopcock is
closed and add a few ml of petroleum (pet) ether to the column. Open the stopcock slightly to
allow some solvent to pass (into a collection vessel) clearing out any major air bubbles trapped in
the glass wool or sand layers. Close the stopcock to leave 1-2 in. of solvent above the sand. In
another vessel, prepare a slurry of 30 g of neutral alumina in pet ether. While allowing the column
to drain very slowly, add the alumina slurry to the column via a short stem pipette. Gentle tapping
of the walls of the column will help the formation of a uniform, air-free alumina packing. Once all
the alumina has been delivered to the column and has begun to settle, allow the solvent to drain
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faster until the solvent level in the column is about 1 cm above the top of the alumina layer.
{NEVER ALLOW THE SOLVENT LAYER TO DROP BELOW THE ALUMINA LAYER
because air channels will develop in the alumina which ruin the column's separation efficiency.}
Add .5 cm of clean sand on top of the alumina layer.
(ii) Delivering the sample to the column: Run the solvent level in the column to just below (~1 mm) the
top of the upper sand layer. Dissolve/suspend (it may not all dissolve) the crude reaction product in
a minimal amount (< 1 ml) of ethyl ether and drip this concentrated solution via pipette directly on
to the sand in the column. Rinse the container with a few drops of ether and add these drops to the
column. Run the sample solution just on to the alumina phase, add ~1 ml of pet ether, and run the
solvent level to just below the top of the sand. Repeat the 1 ml pet ether addition/elusion sequence
1-2 times until the substrate is fully loaded onto the alumina in as compact a band as possible.
(iii) Elution: Now, a larger amount of pet ether may be added to the column to elute the unreacted
ferrocene as a yellow-orange band, collecting it in a small Erlenmeyer flask. Unreacted ferrocene
comes off the column readily with petroleum ether as an eluent but mono-and diacetylferrocene do
not. The amount of unreacted ferrocene obtained will vary from student to student from a clearly
visible amount to none. After all the ferrocene has passed, (this should require less than 20 ml of
pet ether) change the elution solvent to a 2:1 mix of diethyl ether : pet ether to elute the red-orange
acetyl ferrocene product. Collect the pure acetyl ferrocene in a separate Erlenmeyer flask in a
minimal amount of solvent (try not to exceed 20 ml). Transfer the product solution to a round
bottomed flask and remove the solvent in vacuo on the rotory evaporator and then collect and
weigh the dried material.
(C) Product analysis: Analyze the pure (recrystallized and column purified material) and crude
products by silica gel TLC and mp. Compare the TLC results of the crude product with your
purified samples and with authentic ferrocene and acetylferrocene on one TLC slide (elution with
toluene containing a drop or two of ethanol works well usually). Prepare an NMR sample of your
recrystallized product and take to NMR lab for analysis.
Comments: The column packing procedure will be demonstrated at the pre-lab lecture. Both the purity
and the yield of acetylferrocene are to be optimized. The acylation reaction mixture filtrate may be
washed down the drain; the used alumina and all portions of organic solvents should be placed in
the appropriate waste containers in the hoods.
Turn in: completed report sheet; copy of your notebook account; your samples of purified acetyl
ferrocene (recrystallized and chromatographed); TLC's of crude product, purified products, and
authentic ferrocene and acetylferrocene; and 1H-NMR spectrum with peak assignments.
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