Facile purification of iodoferrocene

Article abstract of DOI:10.1021/om2004833

We report a simple method for purifying large amounts of iodoferrocene, synthesized in one step from ferrocene. Halogenated ferrocene derivatives have been known for some time, but are commonly not purified, as obtaining pure samples typically requires multiple steps and often involves use of highly toxic organomercury complexes. The purification described here takes advantage of the increased oxidation potential of iodoferrocene, relative to ferrocene.

Full text of DOI:10.1021/om2004833

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pubs.acs.org/Organometallics
Facile Purification of Iodoferrocene
John C. Goeltz and Clifford P. Kubiak*
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, M/C 0358, La Jolla,
California 92093-0358, United States
ABSTRACT: We report a simple method for purifying large amounts of
iodoferrocene, synthesized in one step from ferrocene. Halogenated
ferrocene derivatives have been known for some time, but are commonly
not purified, as obtaining pure samples typically requires multiple steps and often involves use of highly toxic organomercury
complexes. The purification described here takes advantage of the increased oxidation potential of iodoferrocene, relative to
ferrocene.
Scheme 1. Synthesis and Improved Purification of
’ INTRODUCTION
Iodoferrocene
Ferrocene derivatization is so ubiquitous that many chemists’
first experience with chromatography comes after they find in an
undergraduate laboratory course that the acylation of ferrocene
results in several products.1 Ferrocene, acetylferrocene, and 1,10-
diacetylferrocene readily separate on silica or alumina gel into
three distinct bands. While acylations and similar activations of
ferrocene have allowed chemists to probe ferrocene’s redox
activity in many environments,2ꢀ7 halogenated metallocenes are
often required as synthetic starting materials and have in general
proved more synthetically recalcitrant. Monohalogenated ferro-
cenes are frequently used impure because iodoferrocene and
ferrocene are not easily separated by chromatography, recrystal-
lization, or sublimation. Several two- and three-step syntheses
have been reported, but many of these are unreliable, involve
organomercury reagents, or require the very challenging isolation
of the unstable solid lithioferrocene.8ꢀ14
majority of the ferrocene having been extracted and discarded,
but the organic layer remained yellow-orange in color. Filtration
of the organic layer and removal of the solvent left an orange-
brown oil that solidified into large brown crystals upon standing.
Standard analytical techniques confirmed the purity of the
resulting iodoferrocene (Table 1 and Figure 1).
To demonstrate the utility of pure iodoferrocene, biferrocene
was synthesized by an Ullman coupling.21 The reaction pro-
ceeded in moderate yield, but was highly scalable. This allowed
the production of biferrocene on the gram scale without the use
of mercuric intermediates, useful because acylations and other
reactions of biferrocene tend to proceed in lower yield than
comparable reactions with ferrocene itself. Derivatization of
biferrocene gives a redox probe as well as a mixed valence probe,
where the reorganization energy contributions from the sur-
roundings may be probed spectroscopically and electrochem-
ically.22 The electrochemistry of BiFc in CH2Cl2 is shown
in Figure 2.
In this paper we describe a modified15 one-step preparation of
iodoferrocene (FcI) from ferrocene (Fc) with an improved
purification based on oxidation potentials (Scheme 1). Pure
iodoferrocene allows entry into many coupling reactions, includ-
ing the Ullman,16 Grignard,17 Sonogashira,18 and Suzuki19
couplings, as well as high-purity lithioferrocene in solution via
lithium halogen exchange.20
’ RESULTS AND DISCUSSION
Preparation of iodoferrocene with ferrocene as the major
impurity is achieved by lithiating ferrocene in THF with less
’ CONCLUSIONS
Ferrocene derivatives are commonly used for their redox
activities, but are commonly purified by chromatography or
recrystallization. In the case of iodoferrocene the standard puri-
fication methods are ineffective, but the starting material may be
removed by washing a nonpolar solution of the crude product
with an aqueous solution of a mild oxidant, FeCl3. The resulting
product gives satisfactory elemental analysis and cyclic voltam-
metric responses. The purification is highly scalable (performed
t
than one equivalent of BuLi, then treating the resulting red
solution with solid iodine. After workup, 1H NMR spectra gave a
composition of ∼1.5:1 Fc/FcI for the crude product. Cyclic
voltammetry in CH2Cl2 revealed that iodoferrocene has an
oxidation potential 170 mV more positive than the ferrocene
impurity (Figure 1).
When the crude product was dissolved in hexane and treated
with FeCl3 dissolved in water, the yellow aqueous layer turned
blue-green, consistent with ferrocenium chloride partitioning
into the aqueous layer. As this was repeated, the aqueous layer
eventually ceased to take on a green color, consistent with the
Received: June 6, 2011
Published: June 24, 2011
r
2011 American Chemical Society
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Figure 1. Cyclic voltammetry of the crude reaction product, a mixture
of ferrocene and iodoferrocene (black solid line), and purified iodofer-
rocene (red dashed line) in CH2Cl2 with 0.1 M Bu4NPF6. The working
electrode was a glassy carbon disk, the counter electrode was a platinum
wire, and the reference electrode was Ag/AgCl. The scan rate was 100
mV/s, and potentials are reported versus the ferrocene/ferrocenium
couple.
Figure 2. Cyclic voltammetry of ∼1 mM biferrocene (BiFc) in CH2Cl2
with 0.1 M Bu4NPF6. The working electrode was a glassy carbon disk,
the counter electrode was a platinum wire, and the reference electrode
was Fc/Fc+. The scan rate was 100 mV/s.
room temperature, the reaction was cooled again in an ice bath, and
1 mL of deionized water was added carefully to quench any additional
reactive species. Additional water (25 mL) was added, and the reaction
was stirred for 10 min. After the addition of hexanes (300 mL), the
mixture was washed once with water and three times with aqueous
sodium thiosulfate. The organic layer was dried over MgSO4 and filtered
through Celite. The solvent was then removed using a rotary evaporator
at 30 °C. 1H NMR spectra of the crude reaction product exhibited a ratio
of ∼1.5:1 ferrocene/iodoferrocene with no other metallocene or aro-
matic impurities.
The crude product was taken up in pentane and repeatedly washed
with a saturated aqueous solution of FeCl3 until the aqueous layer no
longer took on the blue-green color of ferrocenium. Vigorously stirring
the biphasic mixture in a flask with a magnetic stir bar and stir plate
between separatory funnel separations quickened the extractions. The
organic layer was dried over MgSO4 and filtered through Celite. The
solvent was then removed using a rotary evaporator at room tempera-
ture. The resulting orange-brown oil solidified upon standing. Yield:
7.03 g (22.5 mmol, 28% yield based on ferrocene) of pure iodoferrocene.
1H NMR (CDCl3): δ (ppm) 4.40 (t, 2H, J = 1.72 Hz), 4.18 (s, 5H), 4.15
(t, 2H, J = 1.72 Hz). Anal. Calcd (found) for C10H9FeI: C, 38.5 (38.7);
H, 2.9 (3.3); N, 0.0 (0.0).
Biferrocene (BiFc) (ref 21). Copper bronze (90:10 Cu/Sn) was
activated23 before use. Powdered bronze (1.17 g) was swirled with a 2%
iodine solution in acetone (1.46 g iodine, 78.44 g acetone). The solid
turned gray. It was vacuum filtered through a #1 filter paper, scraped into
a new flask, and stirred for 10 min with acetone (25 mL) and con-
centrated HCl (25 mL). The material was filtered through a fine frit to
give a fine bronze powder, which was stored in a vacuum desiccator
until use.
An oven-dried 100 mL Schlenk flask was flushed with N2 while
cooling, then charged with iodoferrocene (81 mg, 0.26 mmol orange-
brown solid) and activated copper bronze (350 mg). The solids were
mixed with a spatula. The flask was stoppered with a septum, and a gentle
flow of N2 through the Schlenk flask inlet was maintained. The reaction
was slowly heated to 100 °C in an oil bath. Ferrocene (as a byproduct)
was observed subliming onto the sides of the flask. After 20 h at 100 °C,
the reaction was allowed to cool to room temperature. The majority of
the sublimed ferrocene was rinsed out of the flask with hexanes. The
desired product was extracted from the remaining solid mass into hot
toluene by mixing with a spatula and sonicating the suspension before
Table 1. Calculated and Experimental Elemental Analyses for
Iodoferrocene and Biferrocene
compound
%C
%H
%N
iodoferrocene (FcI), calculated (found) 38.5 (38.7) 2.9 (3.3) 0.0 (0.0)
biferrocene (BiFc), calculated (found) 64.9 (64.5) 4.9 (5.3) 0.0 (0.0)
here on the 15 g scale) and allows for a wide array of further
reactivity and derivatization of the ferrocenyl moiety.
’ EXPERIMENTAL SECTION
General Considerations. Unstabilized THF was distilled from
sodium benzophenone before use. Unstabilized CH2Cl2 was sparged
with argon and passed over neutral alumina before use in electrochem-
istry. Copper bronze was activated as described below.23 All other
materials were used as received. Bu4NPF6 was recrystallized from
methanol and dried at 80 °C under vacuum overnight before use.
NMR spectroscopy was performed on a 500 MHz JEOL spectrometer.
Electrochemistry was performed with a BAS CV50 potentiostat, a glassy
carbon working electrode, a platinum wire counter electrode, and either
a Ag/AgCl or Fc/Fc+ reference electrode. Elemental analyses were
performed by Numega Resonance Laboratories, San Diego, CA.
Iodoferrocene, FcI (ref 15). An oven-dried 500 mL three-neck
flask was purged with argon while cooling, charged with a PTFE-coated
stir bar and ferrocene (14.98 g, 80.5 mmol), and sealed with two septa
and an inlet adapter with a stopcock. The ferrocene was dried under mild
vacuum in the flask (∼1 Torr) overnight. After refilling with argon,
100 mL of THF (freshly distilled from Na/benzophenone) was added
via cannula, and the orange mixture was stirred. One septum was
replaced with an oven-dried addition funnel, and 38 mL of 1.7 M tBuLi
in pentane (64.6 mmol, 0.8 equiv) was added to the funnel via cannula.
The reaction was cooled in an ice bath, tBuLi was added dropwise over
20 min with efficient stirring, and the reaction turned a vibrant red color.
After 15 additional minutes of stirring in the ice bath, the reaction was
cooled in a dry ice/acetone bath. Solid iodine (20.0 g, 78.8 mmol) was
added under an argon flush. The reaction was slowly allowed to come to
room temperature by not adding additional dry ice to the bath. Once at
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filtering off the bronze five times. The crude product was run through an
alumina plug with hexanes as eluent (though ferrocene and biferrocene
can also be purified by vacuum sublimation at increasing temperatures,
∼160 °C at ∼1 mTorr for BiFc). Yield: 16.2 mg (0.044 mmol, 34%).
(Note: this reaction is readily scalable and has been successfully
performed on the 13 g scale.) 1H NMR (CDCl3): δ (ppm) 4.36
(t, 4H, J = 1.72 Hz), 4.18 (t, 4H, J = 1.62 Hz), 4.00 (s, 10H). Anal.
Calcd (found) for C20H18Fe2: C, 64.9 (64.5); H, 4.9 (5.3); N, 0.0 (0.0).
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ckubiak@ucsd.edu.
’ ACKNOWLEDGMENT
The authors thank Dr. Anthony Mrse at the UCSD NMR
Facility and gratefully acknowledge support from NSF CHE-
0616279.
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