Acetylation of Ferrocene: Electrophilic Aromatic Substitution

Acetylation of Ferrocene:
Electrophilic Aromatic Substitution; Column Chromatography
Ferrocene is a yellow organo metallic compound that consists of a complex
formed between ferrous ions (Fe2+) and two cyclopentadienyl anions. As you know from
the organ ic lecture class, the cy clopentadienyl anion is an unusually stable carbanion,
because its -electron structure is aromatic. Since it is aromatic and, in addition, more
electron-rich than b enzene, the cyclopentadienyl anions in ferrocene can undergo a
variety of electrophilic aromatic substitution reactions. The products of these reactions
have a var iety of different colors, as a result of changes in the energy levels of their 
bonds.
As an exa mple of this type of chemistry, you will react ferrocen e with acetic
anhydride in the presence of phospho ric acid to produce acetyferrocen e as the main
product, together with some diacetylferrocene as a by-product. You w ill then purify the
acetylferrocene by chromatography on an alumina column, in order to separate it from
unreacted ferrocen e, and from the diacetylferrocene and other polymeric by-products.
Finally, you will characterize the purified acetylferrocene by TLC, IR, and melting point.
O
O
O
O
CH3
H3C
O
Fe2+
H3PO4
CH3
CH3
Fe2+
+
Fe2+
O
CH3
Mechanism
In your prelab write-up, include a detailed mechanism for (i) formation of the
electrophile in the reaction, and (ii) the electrophilic aromatic substitution reaction.
Pre-Lab Review
This experiment will require you to prepare an alumina column, using the dry
packing method, and to perform TLC, IR and melting point analyses. Be sure to review
all of these procedu res before the lab. In particular, review Operations 21 and 22 in
detail, focusing on the preparation and operation of a column (pp. 707-720), and the
principles underlying the separation methods on alumina and silica gel columns and TLC
plates (pp. 720-728). Your pre-lab write-up should include a detailed procedu re for
packing the column, and a diagram of the column.
Hazards
1. Ferrocene and (especially) acetylferrocene are toxic substances . The main
dange rs are inhalation and absorption through the skin. Follow standard practice for
safety during all procedu res. Wear gloves and wor k in the hood. Do not lean into the
hood and do not rest any part of your body or your lab notebook (or anything e lse that
you may later touch with ungloved hands) aga inst hood surfaces.
2. You w ill also work with petroleum ether (pet ether) and diethyl ether, which
are high ly flammable. Keep these solvents away from hot surfaces.
3. Alumina (in your column) and silica gel (on the TLC plates) are
microparticulate and ea sily beco me airborne, and are hazardous when inhaled. Keep the
alumina in a covered container when you are carrying it through the lab, and only work
with it in the hoods. Work with the TLC plates in the hoods as much as possible, and try
not to scrape the surface material off the TLC plates if you are ex amining them out of the
hoods. Clean up any spills. Dispose of all column materials and TLCs in the solid
waste container when you are finished.
Experimental Proce dure
This procedu re is adap ted from a method described in the Journal of Chemical
Education. The reference is: Richard E. Bozak, J. Chem. Ed. 43, 73 (1966 ).
1. Add 1.5 g ferrocene (MW = 186.03) to 5 mL acetic anhydride in a clamped roundbottom flask. Stir using a magne tic stir bar. (Note: the boiling point of acetic anhydride
is 138-140 °C, d = 1.08 g/ mL, MW = 102.09 )
2. Add approximately 1.0 mL 85% (w/v) phosphoric acid (MW H 3PO4 = 98.00)
dropwise to the stirring ferrocene solution. Then cap the flask with a rubber septum and
attach a drying tube con structed from a syringe and need le, following your TA's
instructions. Heat the reaction mixture in a boiling wa ter bath (also stirred) for 10 min. at
boiling point. Then remove the water bath and cool the reaction mixture for a few
minutes by stirring it in a water bath at RT. Return your hot plate to the cabinet as
soon as possible, to avo id having its hot surface around when you prepare and run
your column.
3. Pour the coo led reaction mixture into a 50 mL beake r containing 20 g of crushed ice.
Add solid sodium bicarbonate to the resulting mixture un til a pH of about 6-7 is attained.
Then ch ill the mixture in an ice bath for a further 30 min. (at least), while you prepare
your alumina column. In your prelab write-up, you should estimate how much sodium
bicarbonate will be needed for this step.
4. Prepare an alumina column using petroleum ether (pet ether) as the solvent, following
the dry packing method described in the Lehman book (2nd edition, p. 713). Use
approximately 10 g of the neutral alumina provided in the reagen ts hood (Brockman
activity I, 60 - 325 mesh). Do not weigh the alumina. Instead, measure it by volume in
a small beake r (approx. 10 mL).
5. Once your column is ready for use, return to the reaction mixture. Collect the solid
brown precipitate
by vacuu m filtration, and wash it with small amounts of chilled water. Then dry the solid
for a further 10-15 min. by leaving it on the filter paper and using con tinued suction.
Column chromatography works on the
same principle as TLC
• The adsorbent
(alumina or silica gel)
should be packed with
a stream of air or
nitrogen to drive out
air pockets in the
column. This leads to
better separation.
Selection of the eluting solvent is an
important factor in a good separation
• The more polar the
eluant, the faster
compounds will move
through the column.
If a solvent is too
“fast”, everything will
come out with the
solvent front.
More polar compounds travel more
slowly through the column.
• Compounds with more
polar groups will
adhere to the
adsorbent (alumina or
silica gel) more
strongly than less
polar molecules.
The column should have a level surface so
that the bands stay even as they travel through
the column.
• The sample should be
applied to the column
in a minimum amount
of solvent. Wide band
widths lead to poor
separation.
• Narrow bands
traveling through the
column prevent
overlap.
Isolating the separated compounds
• Run TLC’s of the
fractions after the
column to decide
which ones to
combine.
6. Weigh the crude product scraped off the filter paper. Then take a 0.4 g portion of this
material and dissolve it in about 1-2 mL of toluene (some material will not dissolve).
Load the toluene solution onto the alumina column, including any insoluble material,
following the procedure described in your book and by your TA. Then e lute your column
using 20-50 mL aliquots of (a) pet ether only, followed by (b) 20% diethyl ether in pet
ether, and then (c) 50% diethyl ether in pet ether. Never let the column run dry.
Any unreacted ferrocene (yellow) should be eluted in the first or second fractions. The
acetylferrocene product will elute after the ferrocene as an orange-red solution. Collect
this solution as it elutes from the co lumn. (You may also see a second orange -red
component at the top of the column that elutes much more slowly than the
acetylferrocene . This is the diacetylferrocene by-product, and it can also be eluted and
collected, if you use 100% diethyl ether, if you wish to analyze it later by TLC.)
NOTE: (a) Do not throw any of your column eluate away, until you have identified the
acetylferrocene by a TLC comparison with authentic acetylferrocene (see below).
(b) If the flow rate of your column is too slow, you can carefully apply air pressure to the
top of the column to increase the flow rate. This should not cau se any problems, and
often gives better separations, provided you take care nev er to let the co lumn run dry.
7. Iden tify the eluting fraction that contains acetylferrocene, by running a TLC of the
eluate (the acetylferrocene should be orange -red, and will probably be in the 50% diethyl
ether fraction). Choose a solvent to elute your TLC that makes sense, based on your
observations of the column chromatography. The elution characteristics of ferrocene and
its derivatives on alumina (your column) and silica gel (your TLC) are very similar. On
the TLC, compare your eluted product to the crude material you loaded onto the column
and to a sample of authentic acetylferrocene. Use diethyl ether as the solvent for the
other two TLC samples. Report your TLCs as diagrams drawn in your notebook,
complete with Rf measurements. Do not tape these TLCs in your book, since the
compounds are toxic and the silica gel will flake off the plate.
8. When you have identified the fraction containing your purified acetylferrocene,
remove the solvent by rotatory evaporation. Scrape the solid from the flask and weigh it.
Then obtain an IR spectrum as a Nujol mull or paste (use a very small drop of "Nujol", or
mineral oil). Measure the melting point of your product after drying it in your desiccator
for a week. Report all of your measurements, and wr ite a conclusion that assesses the
evidence for the correct identity of your product, its percent yield (in molar terms), and
its purity. When ca lculating your yield, remember to account for the fact that you only
purified a fraction of your product.
Exercise Questions
1. (a) What is the molar ratio of acetic anhydride to ferrocene used in your reaction? (b)
What is the molar ratio of phosphoric acid to ferrocene used, assuming you added 1.0 mL
of the 85% (w/v) acid?
2. Do you expec t the acetylated cy clopentadienyl anion to be more reactive or less
reactive towards acetylation, compared to the underivatized cyclopentadienyl anion?
Explain.
3. Obtain a copy of the FTIR spectrum of mineral oil (Nujol) from a reliable internet
source, and tape it into your notebook. Label the mineral oil peaks in your IR spectrum
of acetylferrocene .
4. Look a t the NMR spectra of ferrocene and acetylferrocene in this handout. Note the
single sharp peak obtained for ferrocene. (a) Based on the proton-NMR spectrum, do you
expect ferrocen e to be more reactive towards acetylation than benzene or less reactive?
Explain. (b) Sugges t an assignment for the four peaks in the proton-NM R spectrum of
acetylferrocene . Exp lain your assignment.
Expt. 13 – Investigation of a C=O Bond by
Infrared Spectroscopy
Goal: To predict the relationship between
the vibrational frequencies of C=O bonds in
IR spectra and their bond strengths.
Each student will be given one of five
carbonyl-containing compounds. Record
the IR spectrum of your assigned compound
and note the frequency of the C=O stretch at
the point of maximum absorption.
O
O
O
H
N
CH3
H
2-heptanone
heptanal
CH3
N, N-dimethylformamide
O
O
Cl
O
Cl
O
Cl
ethyl butyrate
ethyl trichloroacetate
Prelab:
Each student should (a) come to the lab with
a predicted order of frequencies for these
five compounds, and an explanation for this,
written in your notebooks. (b) convert the
data for each compound into frequencies in
-1
Hz (s ). Discuss differences from your
predictions using the arguments of organic
chemistry. (c) Tape your spectrum into your
lab book.
Write your results
for the carbonyl stretch
-1
frequency (cm ) on the board to share the
data. Predict and discuss your experimental
results and be prepared to modify your
hypothesis about the relationship between
bond strength and IR vibrational frequency.
The C=O bond has some single bond
character.
O
O

O

If Z is an electron-withdrawing group, then
resonance structure 2 becomes less important
O
R
Z
1

O
R
O
Z
R

Z
2
What is the effect on the strength of the
C=O bond?
If Z = nitrogen, resonance structure 3 contributes to the overall
picture.
O
R
O
NH2
1
R
O
NH2
2
R
NH2
3
If Z = oxygen, resonance structure 3 is considerably less
important.
c = 
c = 3 x 108 meters/second
x 1010 centimeters/second
h = Pla nck’s constant
h = 6.63 x 10-34 Joules . sec
frequency
E = h
c
hc
 = wavelength
The wavenumber is the inverse of the
wavelength. It is directly proportional to
energy.
Expt. 16 – Separation of an Alkane Clathrate
Urea forms a tunnel-like channel (a
clathrate) around straight-chain
hydrocarbons with seven or more carbons.
Goal: to see if urea can be used to remove
hexadecane from a mixture of methanol and
2,2,4-trimethylpentane by forming a
clathrate with the straight-chain
hydrocarbon.
hexadecane
negative octane rating
CH3OH
2,2,4-trimethylpentane
octane rating = 107
octane rating = 100
O
H2N
NH2
urea
Expt. 16 – Separation of an Alkane Clathrate
• Preparation: You will add urea dissolved in methanol to
a mixture of 2,2,4-trimethylpentane and hexadecane. After
a white solid forms, cool with an ice/water bath until
crystallization of the clathrate is complete.
Dry and weigh the urea clathrate. Dissolve
the urea in water and extract the hexadecane
into dichloromethane. Dry the organic layer
and then evaporate the solvent. Weigh the
hexadecane. Use this equation to estimate
the number of ureas per hexadecane:
Host/guest ratio for urea clathrates = 1.5 +
0.65n
n = number of carbons in the guest molecule
Confirm identity of the hydrocarbon by
comparison of its IR spectrum to that of
hexadecane and 2,2,4-trimethylpentane
Clathrates in the News
• Methane hydrate deposits
on the ocean floors are
twice the size of the
known coal and gas
reserves on earth. Could
they be tapped as an
energy source? Methane
is a potent greenhouse gas
and could contribute to the
global warming
phenomenon.
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Ph o to - J PEG d e c o m p re s s o r
a re n e e d e d to s e e th i s p i c tu re .
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Ph o to - J PEG d e c o m p re s s o r
a re n e e d e d to s e e th i s p i c tu re .