Transcript Document

Acetylation of Fe rrocene:
Electroph i l ci Aromatic Su bsti tution ; C olum n Chromatography
Ferrocene is a yellow organomet allic compound that consists of a complex
formed between ferrous ions (Fe2+) and two cyclopentadienyl anions. As you knowfrom
the organic lecture class, the cyclopentadienyl anion is an unusually stable carbanion,
because its -elect ron structure is aromat ic. Since it is aromat ic and, in addition, more
elect ron-rich than benzene, the cyclopentadienyl anions in ferrocene can undergo a
variety of electrophilic aromat ic subst itut ion react ions. The product s of these reactions
have a variet y of different colors, as a result of changes in the energy levels of their 
bonds.
As an example of this t ype of chemistry, you will react ferrocene with acet ic
anhydride in the presence of phosphoric acid to produce acetyferrocene as the main
product, together with some diacetylferrocene as a by-product . You will t hen purify the
acet ylferrocene by chromatography onan alumina column, in order to separat e it from
unreacted ferrocene, and from the diacetylferrocene and other polymeric by-products.
Finally, you will characterize the purified acetylferrocene by TLC, IR, and melt ing point.
O
O
O
O
CH3
H3C
O
Fe2+
CH3
CH3
Fe2+
+
Fe2+
O
H3PO4
CH3
Mech an i sm
In your prelab write-up, include a detailed mechanism for (i) format ion of the
elect rophile in the reaction, and (ii) the electrophilic aromatic subst itution react ion.
Pre-Lab Review
This experiment will require you to prepare an alumina column, using t he dry
packing method, and to perform TLC, IR and melt ing point analyses. Be sure to review
all of these procedures before the lab. In part icular, review Operat ions 21 and 22 in
detail, focusing on the preparation and operat ion of a column (pp. 707-720), and the
principles underlying the separat ion methods on alumina and silica gel columns and TLC
plates (pp. 720-728). Your pre-lab write-up should include a detailed procedure for
packing the column, and a diagram of the column.
Haz ards
1. Ferrocene and (especially) acetylferrocene are toxic subs t ances. The main
dangers are inhalation and absorpt ion through the skin. Follow standard pract ice for
safety during all procedures. W e argloves an d work in the hood. Do not lean into t he
hood and do not rest any part of your body or your lab notebook (or anything else that
you may later touch with ungloved hands) against hood surfaces.
2. You will also work with petroleum ether (pet ether) and diethyl ether, which
are highly flammable. Ke ep these solvents away from hot surfaces.
3. Alumina (in your column) and silica gel (on the TLC plates) are
micropart iculate and easily become 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 T LC plat es in the hoods as much as possible, and try
not to scrape the surface mat erial off the TLC plates if you are examining them out of the
hoods. Clean up any spills. Dispose of all col umn m ate rial s an d TLCs i n the sol id
waste con tainer when you are fin ished.
Experimen tal Procedure
This procedure is adapted from a method described in the Journal of Chemical
Educa tion. 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 magnetic 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 H3PO4 = 98.00)
dropwise to the stirring ferrocene solution. Then cap the flask with a rubber septum and
attach a drying tube constructed from a syringe and needle, following your TA's
instructions. Heat the reaction mixture in a boiling water 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 cabi net as
soon as possible, to avoid h aving its hot surface arou n d when you prepare and ru n
your colum n.
3. Pour the cooled reaction mixture into a 50 mL beaker containing 20 g of crushed ice.
Add solid sodium bicarbonate to the resulting mixture until a pH of about 6-7 is attained.
Then chill 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 reagents hood (Brockman
activity I, 60 - 325 mesh). Do n ot weigh the alumina. Instead, measure it by volume in
a small beaker (approx. 10 mL).
5. Once your column is ready for use, return to the reaction mixture. Collect the solid
brown precipitate
by vacuum 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 continued 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 port ion of this
material and dissolve it in about 1-2 mL of toluene (some material will not dissolve).
Load the toluene solut ion onto t he alumina column, including any insoluble material,
following the procedure described in your book and by your TA. Then elute your column
using 20-50 mL aliquots of (a) pet ether only, followed by (b) 20% diet hyl 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 fract ions. The
acet ylferrocene product will elute after the ferrocene as an orange-red solut ion. Collect
this solut ion as it elutes from the column. (You may also see a second orange-red
component at the top of the column that elutes much more slowly than the
acet ylferrocene. 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 ident ified the
acet ylferrocene by a TLC comparison with authent ic acetylferrocene (see below).
(b) If the flow rate of your column is too slow, you can carefully apply air pressure to t he
top of t he column t o increase the flow rate. This should not cause any problems, and
often gives bet ter separat ions, provided you take care never to let the column run dry.
7. Ident ify the elut ing fract ion that contains acetylferrocene, by running a TLC of the
eluate (t he acetylferrocene should be orange-red, and will probably be in the 50% diethyl
ether fract ion). Choose a solvent to elute your TLC that makes sense, based on your
observat ions of the column chromatography. The elut ion characterist ics 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 authent ic 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 measurement s. Do n ot tape these TLCs in your book, since the
compounds are t oxic and the silica gel will flake off the plate.
8. When you have ident ified the fract ion containing your purified acetylferrocene,
remove the solvent by rotatory evaporat ion. 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 melt ing point of your product after drying it in your desiccat or
for a week. Report all of your measurements, and write a conclusion t hat assesses the
evidence for the correct ident ity of your product , its percent yield (in molar terms), and
its purity. When calculat ing your yield, remember to account for the fact that you only
purified a fract ion of your product.
Ex ercise Q ue stions
1. (a) What is the molar ratio of acetic anhydride t o ferrocene used in your react ion? (b)
What is the molar rat io of phosphoric acid to ferrocene used, assuming you added 1.0 mL
of the 85% (w/v) acid?
2. Do you expect t he acetylated cyclopentadienyl anion to be more react ive or less
react ive towards acetylat ion, compared to the underivat ized cyclopent adienyl 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 t he mineral oil peaks in your IR spectrum
of acetylferrocene.
4. Look at the NMR spect ra 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 ferrocene to be more react ive towards acet ylation than benzene or less reactive?
Explain. (b) Sugges t an assignment for the four peaks in the proton-NMR spectrum of
acet ylferrocene. Explain your assignment.
Expt. 13 – Inv estigation of a C=O Bond by
Infrared Spectroscopy
Goal: To pr edict the relationship be tween
the v ibrational frequencies of C=O bond s in
IR spectra and th eir bond strengths.
Each student will be given one o f five
carbonyl-containing compounds. Record
the IR spectrum of your assigned co mpound
and no te the frequency o f the C=O stretch at
the po int 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 no tebooks. (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 (c m ) on the bo ard to share the
data. Predict and d iscuss your exper imental
results and b e prepared to modify you r
hypo thesis about the relationship between
bond strength and I R 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 o f 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 = Planck’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 A lkane Clathrate
Urea forms a tunnel-like channe l (a
clathrate) around straight-chain
hydro carbons with seven or more carbons.
Goal: to see if urea can b e used to remove
hexadecane from a mixture of methanol and
2,2,4-trimethylpentane by for ming a
clathrate with the straight-chain
hydro carbon.
hexadecane
negative octane rating
CH3OH
2,2,4-trimethylpentane
octane rating = 107
octane rating = 100
O
H2 N
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 w eigh the urea clathrate. Dissolve
the urea in water and extract the hexad ecane
into dichloromethane. Dry the organic layer
and then evapo rate the solvent. Weigh the
hexadecane. Use this equation to estimate
the nu mber of ureas per hexad ecane:
Host/guest ratio for urea clathrates = 1.5 +
0.65n
n = nu mber of carbons in the gue st 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.
Qu i c k T i m e ™ a n d a
Ph o t o - J P EG 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 t u re .
Qu i c k T i m e ™ a n d a
Ph o t o - J P EG 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 t u re .