NOTE 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.
’ INTRODUCTION 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,27 halogenated metallocenes are often required as synthetic starting materials and have in general proved more synthetically recalcitrant. Monohalogenated ferrocenes are frequently used impure because iodoferrocene and ferrocene are not easily separated by chromatography, recrystallization, 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.814 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, including 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 than one equivalent of tBuLi, 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 r 2011 American Chemical Society
Scheme 1. Synthesis and Improved Purification of Iodoferrocene
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 orangebrown 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 proceeded 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 surroundings may be probed spectroscopically and electrochemically. 22 The electrochemistry of BiFc in CH2Cl2 is shown in Figure 2.
’ 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 purification 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 voltammetric responses. The purification is highly scalable (performed Received: June 6, 2011 Published: June 24, 2011 3908
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Figure 1. Cyclic voltammetry of the crude reaction product, a mixture of ferrocene and iodoferrocene (black solid line), and purified iodoferrocene (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.
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 electrochemistry. 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
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 aromatic 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 temperature. The resulting orange-brown oil solidified upon standing. Yield: 7.03 g (22.5 mmol, 28% yield based on ferrocene) of pure iodoferrocene. 1 H 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 concentrated 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 orangebrown 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 3909
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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:
[email protected].
’ ACKNOWLEDGMENT The authors thank Dr. Anthony Mrse at the UCSD NMR Facility and gratefully acknowledge support from NSF CHE0616279. ’ REFERENCES (1) Gilbert, J. C.; Monti, S. A. J. Chem. Educ. 1973, 50, 369. (2) Creager, S. E.; Rowe, G. K. J. Electroanal. Chem. 1994, 370, 203. (3) Chidsey, C. E. D. Science 1991, 22, 919. (4) Gryko, D. T.; Zhao, F.; Yasseri, A. A.; Roth, K. M.; Bocian, D. F.; Kuhr, W. G.; Lindsey, J. S. J. Org. Chem. 2000, 65, 7356. (5) Eckermann, A. L.; Meade, T. J. Coord. Chem. Rev. 2010, 254, 1769. (6) Astruc, D. Electron Transfer and Processes in Transition-Metal Chemistry; Wiley-VCH: New York, 1995. (7) Galloway, C. P.; Rauchfuss, T. B. Angew. Chem., Int. Ed. Engl. 1993, 32, 1319. (8) Dodo, T.; Suzuki, H.; Takiguchi, T. Bull. Chem. Soc. Jpn. 1970, 43, 288. (9) Butler, I. R.; Wilkes, S. B.; McDonald, S. J.; Hobson, L. J.; Taralp, A.; Wilde, C. P. Polyhedron 1993, 12, 129. (10) Wright, M. E. Organometallics 1990, 9, 853. (11) Fish, R. W.; Rosenblum, M. J. Org. Chem. 1965, 30, 1253. (12) Davison, A.; Rudie, A. W. Synth. React. Inorg. Met.-Org. Chem. 1980, 10, 391. (13) Bildstein, B.; Malaun, M.; Kopacka, H.; Wurst, K.; Mitterb€ock, M.; Ongania, K.-H.; Opromolla, G.; Zanello, P. Organometallics 1999, 18, 4325. (14) Morrison, W. H.; Hendrickson, D. N. Inorg. Chem. 1972, 11, 2912. (15) Rebiere, F.; Samuel, O.; Kagan, H. B. Tetrahedron Lett. 1990, 31, 3121. (16) Rausch, M. D. J. Org. Chem. 1961, 26, 1802. (17) Shechter, H.; Helling, J. F. J. Org. Chem. 1961, 26, 1034. (18) Plenio, H.; Hermann, J.; Sehring, A. Chem.—Eur. J. 2000, 6, 1820. (19) Mamane, V. Mini-Rev. Org. Chem. 2008, 5, 303. (20) Koray, A. R.; Ertas, M.; Bekaroglu, O. J. Organomet. Chem. 1987, 319, 99. (21) Rausch, M. D. J. Am. Chem. Soc. 1960, 82, 2080. (22) Dong, T.-Y.; Chang, L.-S.; Tseng, I. M.; Huang, S.-J. Langmuir 2004, 20, 4471. (23) Vogel, A. I. A Text-Book of Practical Organic Chemistry, 3rd ed.; Longman Group, Ltd.: London, 1956.
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