Acetylation of Ferroc ene:
Electro phili c Aroma tic Subs titution; Column Chromatogra phy
Ferrocene is a yell ow organo metalli c compound that consists of a complex
formed between ferrous ions (Fe2+) and two cyclop entadieny l anions. As you know from
the organ ic lecture class, the cy clopentadieny l anion is an unu suall y stable carbanion,
because it s -electron struc ture is aromatic. Since it i s aromatic and , in addit ion , more
electron-rich than b enzene , the cyc lopentadieny l anions in ferrocene can und ergo a
variety o f electrophili c aromatic subs tit ution reactions. The p roduc ts of these reaction s
have a var ie ty of dif ferent colors, as a result of changes in the ene rgy le vels of their 
bonds .
As an exa mple of this typ e of chemistry, you w ill react ferrocene wit h acetic
anhyd ride in the p resence of phospho ric acid to produce acetyferrocene as the main
produc t, toge ther wit h some dia cetylferrocene as a by-p roduc t. You w ill then purify the
acetylf errocene by ch romatography on an alumina column, in o rder to separate it from
unreacted ferrocene, and from the diacetylferrocene and other polymeric by-products.
Finall y, you w ill char acterize the purified acetylf errocene by TLC, IR, and melti ng po int.
O
O
O
O
CH3
H3C
O
Fe2+
CH3
CH3
Fe2+
+
Fe2+
O
H3PO4
CH3
Mechanism
In you r prelab writ e-up, include a detail ed mechan ism for (i) formation of the
electrophil e in the reaction , and (ii ) the electrophili c aromatic subs tit ution reaction.
Pre-Lab Review
This exper im ent will require you to prepare an alumi na column, using the dry
packing method, and to perform TLC, IR and melti ng po int ana lyse s. Be sure to review
all of t hese procedures before the la b. In pa rticular, review Operations 21 and 22 in
detail, focus ing on the preparation and operation o f a column (pp. 707-720), and the
principles unde rlying the separation methods on a lumi na and sili ca ge l columns and TLC
plates (pp. 720-728). Your pre-lab writ e-up should include a detailed procedure for
packing the colu mn, and a diagr am of the column.
Hazar ds
1. Ferrocene and (especiall y) acetylf errocene are toxic subs tances . Th e main
dange rs are inh alation and absorption through the skin. Follow stand ard practice for
safety during all procedures. Wear gloves and wor k in the hood. Do not lean into the
hood and do not rest any p art of you r body or your lab no tebook (or any thing e ls e that
you may later touch wit h ung loved hand s) aga inst hood surfaces.
2. You w il l also work wit h petroleum ether (pet ether ) and diethyl ether, which
are high ly fla mma ble. Keep these solvents away from hot surfaces.
3. Alumina (in you r column) and sili ca ge l (on the TLC plates) are
mi croparticula te and ea sily become air borne , and are haza rdous when inha led. Keep the
alumi na in a cove red cont ainer when you a re carrying it through the lab, and on ly work
wit h it i n the hoods . Work with the TLC plates in the hood s as mu ch as possible, and try
not to scrape the surface material off the TLC plates if you are examining them out of the
hoods . Clean up any spil ls. Dispose of all column materials and TLCs in the solid
waste container when you are finished.
Experimental Proce dure
This procedure is adapted from a method d escribed in the Journal of Chemi cal
Educa tion. The reference is: Ric hard E. Bozak , J. Chem. Ed. 43, 73 (1966 ).
1. Add 1.5 g ferrocene (MW = 186.03) to 5 mL acetic anhyd ride in a clamped round bottom flask. Stir using a magne tic stir bar. (Note: t he bo ili ng point of acetic anhyd ride
is 138-140 °C, d = 1.08 g/ mL , MW = 102.09 )
2. Add approxim ately 1 .0 mL 85% (w/v) pho sphor ic acid (MW H 3PO4 = 98.00)
dropwise to the stirring ferrocene solution. Then cap the fl ask wit h a rubb er septum and
attach a drying tub e constructed from a syringe and need le, foll owing you r TA's
instructions . Heat the reaction mi xtu re in a boili ng wa ter bath (also stir red) fo r 10 mi n. at
boili ng po int. Then remov e the water bath and cool the reaction mi xture for a few
mi nutes by stirring it in a water bath at RT. Return your hot plate to the cabinet as
soon as possible, to avoid having its hot surface aro und when you prepare and run
your column.
3. Pour the cooled reaction mixture into a 50 mL beaker containing 20 g o f crush ed ice.
Add soli d sodium bicarbona te to the resulti ng mi xture un til a pH of abou t 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 you r prelab writ e-up, you shou ld estim ate how much sodium
bicarbona te wil l be needed for this step.
4. Prepare an alumi na column u sing pe troleum ether (pet ether) as the solven t, foll owing
the dry packing method de scribed in the Lehman book (2nd edition, p. 713). Use
approximately 10 g o f the neu tral alumi na provid ed in the reagen ts hood (Brockman
activit y I, 60 - 325 mesh). Do not 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 mi xture. Collect the soli d
brown p recipit ate
by vacuu m filt ration, and wa sh it w ith small amounts of chill ed water. Th en dry the soli d
for a further 10-15 mi n. by le aving it on the filt er 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 p roduc t scraped off t he filt er paper. Then take a 0.4 g portion of this
material and dissolve it i n abou t 1-2 mL of toluene (some material will not dis solve).
Load the toluene solution on to the alumi na column, including any inso luble material,
following the procedure de scribed in you r book and by you r TA. Then e lute you r column
using 20-50 mL ali quots of (a) pet ether only, foll owed by (b) 20% die thy l ether in pet
ether, and then (c) 50% diethyl ether in pet ether. Never let the column run d ry.
Any unre acted ferrocene (ye ll ow) shou ld be eluted in the fir st or second fractions . The
acetylf errocene produc t will elute after the ferrocene as an o rang e-red solution. Collect
this solution as it elutes from t he co lumn. (You may also see a second orange -red
componen t at the top of the column that elutes much more slowly than the
acetylf errocene . Th is is the d iacetylferrocene by-produc t, and it can als o be eluted and
coll ected, if you use 100% diethyl ether, if you wis h to analyze it later by TLC.)
NOTE: (a) Do no t throw any of your column e luate away, un til you have identifi ed the
acetylf errocene by a TLC comparison with authen tic acetylf errocene (see below).
(b) If the flow rate of you r column is too slow, you c an carefull y app ly air pressure to the
top of the column to increase the flow rate. This shou ld not cause any problems, and
often g ives better separations, provided you take care nev er to let the co lumn run dry.
7. Iden tif y the eluting fraction that contains acetylf errocene, by runn ing a TLC of the
eluate (the acetylferrocene shou ld be orange -red, and will probably be in the 50% diethyl
ether fraction). Choose a solven t to elute you r TLC that makes sense , based on your
observa tions of the column chro matography . The elution cha racteristics of ferrocene and
it s derivatives on alumi na (you r column ) and sil ica gel ( your TLC) are very simil ar. On
the TLC, compare your eluted produc t to the crude material you loaded onto the column
and to a sample of authen tic acetylf errocene. Use diethyl ether as the solven t for the
other two TLC samples. Report your TLCs as diagra ms drawn in you r no tebook,
complete wit h R f m easurements. Do not tape these TLCs in you r book, since the
compound s are toxic and the sil ica gel w ill flake off the plate.
8. When you have identified the fraction containing your purified acetylf errocene,
remove the solvent by rotatory ev aporation. Scrape the soli d from the flask and weigh it .
Then ob tain an IR spectrum as a Nujol mull or paste (use a very small drop of "Nujol", or
mi neral oil) . Measure the melti ng point of you r produc t after drying it in you r desiccator
for a week. Report all of your measure me nts, and wr it e a conc lusion that assesses the
evidenc e for the correct identit y o f you r produc t, it s percent yie ld (in molar terms), and
it s pur it y. When ca lculating you r yield, remember to account for the fact that you only
purified a fraction o f your produ ct.
Exercise Questions
1. (a) What is the molar ratio of acetic anhyd ride to ferrocene used in your reaction? (b)
Wha t is the molar ratio of phospho ric acid to ferrocene used , assumi ng you add ed 1.0 mL
of the 85% (w/v) acid?
2. Do you expec t the acetylated cyclopentadieny l anion to be more reactive or less
reactive towards acetylation, compared to the und erivatized cyc lopentadienyl anion?
Expl ain.
3. Obtain a copy o f t he FTIR spectrum of mi neral oil (Nujol) from a reli able internet
source, and tape it into your notebook. Label the mi neral oil peaks in you r IR spectrum
of acetylferrocene .
4. Look a t the NMR spectra of ferrocene and acetylferrocene in this handou t. Note the
single sharp peak ob tained for ferrocene. (a) Based on the proton-NMR spe ctrum, do you
expe ct ferrocene to be more reactive towards acetyla tion than b enzene or less reactive?
Expl ain. (b) Sugges t an assignment for the four peaks in the p roton-NMR spectrum of
acetylf errocene . Exp lain your assignment.
Expt. 13 – Inv estigation 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 o f five
carbonyl-containing compound s. Record
the IR spectrum of your assigned compound
and no te the frequency o f 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 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 r esults
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 you r
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 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 tunne l-like channe l (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 for ming 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 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 number 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.
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