An Enhanced Chromatographic Technique for the Preparative Scale Purification of Acetyl Ferrocene James Davis and D. Huw Vaughan Department of Chemistry and Chemical Engineering, Sensors Group, University of Paisley, High Street, Paisley, Scotland PA1 ZBE, UK Marco F. Cardosi Department of Biology, Sensors Group, University of Paisley, High Street, Paisley, Scotland PA1 2BE, UK Acetyl ferrocene serves not only as the starting material for a large number of ferrocene derivatives, but also it has a varied range of properties that make it suitable for incorporation into undergraduate laboratory courses (1).Its use in such courses, however, has been limited by the time-consuming problem of purifying significant quantities of the material. The small-scale preparation of acetyl ferrocene and its subsequent analysis by several chromatographic techniques, including liquid column ( 2 , 3 ) ,thin layer (41, high performance liquid (5, 6)and dry column chromatography (7),have been well documented. These reports have been invaluable in demonstrating the ability of chromatography to study the course of the acetylation reaction and to the identification of the reaction products. However, almost all of the previously mentioned techniques are unsuitable for the large preparative scale purification of this versatile compound. High performance liquid chromatography would have been the method of choice but the microliter scale volumes are a major restriction and although simple liquid column procedures are more common to preparati;e scale separations they are unfortunately extremely slow, with several hours needed to elute even modest amounts of the compound. To overcome this problem we have developed a variation of flash column chromatography that can reduce dramatically the elution time of the various fractions. from the normal period of several hours to a matter of minutes, and which ltilizes standard laboratorv glassware. In this modified chromatographic technique, suction (by means of a water pump) to the bottom of the . . is applied .. column allowing the two fractions, corresponding to the the product acetyl ferrocene and unreacted ferrocene, to be eluted cleanly and rapidly. The apparatus used in the purification mocess is detailed in the firmre and consists of a 100-mL separating funnel with a glass wool plug. The funnel is filled with a s l u m of silica eel' orepared using the etherlethyl acetate mixture descriied be&, leavingjust enough suace a t the to^ . to .lace the crude acetvl ferrocene. The column is connected to a water pump via a trap with 250-mL conical flasks serving a s the collecting vessels. The solvent mixture used to elute the unreaded ferrocene was 96% ~etroleumether (40-60 " C )and 4% ethvl acetate (bv . . volume). The acetyl derivative can be eluted speedily using pure ethyl acetate. u
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Preparation of Acetyl Ferrocene Caution: Protective gloves should be worn when handling these reagents. Ninety percent phosphoric acid (1.5 mL) is slowly added to a stirred solution of ferrocene (1.5 a) and acetic anhvdride 15 mL conteined in a 100-mL round hortomsd f l a s ~ . Thc flask la rhcn fitted with a calc~umchloride w a r d tub(! and placed in a water bath maintained a t 50 "C. After a period of 10 min, the mixture is removed and poured into a 0.25 M sodium acetate solution. The resulting mixture is cooled in ice and 50 mL of dichloromethane added.
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'The ab ily lo regenerate tne colmn means tnal it neea on y oe al ows I prepared once dur ng a normal acaaem c lerm Tn s fcat~re to be constructed bva technician, thus removing the risk of students being exposed to the silica gel powder and the problems associated with its handling and disposal. Caution: In the event of students being permitted to prepare the packing material, they should be made aware ofthe hazards involved in handline the fine oowder and should take the proper precautions.
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The preparation of the acetyl derivative is well documented (2-7) b u t we have found that by modifyi n g several previously published methods we can minimize the format i o n of intractable t a r s caused by decomposition produ c t s , t h e r e b y prolonging the life of the column. If another route is used in the preparation of t h e crude material. care To water should be t a k k n to J b p Pump avoid the ~roduction of the decomposition products, the diacetyl a n d o t h e r byproducts, Chromatography apparatus.
Journal of Chemical Education
C a u t i o n : Cnrc ihoulo hc rnkcn when handling the .ulvt.nts. c,prcinllg d~chloromclhnnc,2nd thcir u?e. where pc+ciblt. should he rc;triclcd t o n n cfficcnl fume hood. The orange organic layer is separated and retained and the dark, brown-colored aqueous layer washed with a further 20 mL of dichloromethane. The organic fractions are combined and aash(vl with wlter liillowrd bv saturated so'lht:orannic li~verir dried with dium bici~rl~matc ;i~~luti(~n. anhydrous magnesium sulfate a n l t h e c&le acetyl derivative obtained bv removal of the solvent on a rotarv evavo-
Aslurry of the crude acetyl ferrocene (approx. 1g) is prepared using the petroleum etherlethyl acetate solvent mix-
ture and placed on top of the column. Aquick-fit cylinder is then added and filled with solvent. The separating funnel valve i s opened and the water pump activated. Then the yellow of the unreacted ferrocene will move rapidly down the column. The rate of elution can be controlled by manipulating either the air valve connected to the trap or the water tap directly, although the latter method is not recommended i n ease of water suck back. Once the yellow of the ferrocene is no longer present on either the column or in the eluant stream the collectinp - vessel should be replaced, in preparation for collecting the acetyl derivative. The solvent svstem also is changed to uure ethyl acetate instead of the petroleum ether kixture. suction is reapplied and the red band due to the acetyl derivative removed from the column. When both fractions have been collected, the silica gel may be regenerated by passing 100 mL of the petroleum etherietbyl acetate mixture through the column. The acetyl derivative is obtained by removing the solvent on a rotary evaporator with the purity being quickly determined by thin-layer chromatography on silica strips using a petroleum ether (90%)/ethyl acetate (10%) solvent mixture, with one spot due to the product being observed. Conclusion The majority of undergraduate laboratoq. experiments involving acetyl ferrocene have focused on the small-scale
preparation and chromatographic identification of the reaction products. The experiments described by Vogel (11, however, have shown that this compound is far more versatile and aoolicable to a wide range of chemical tooics .. from simple acid-base behavior to cyclic voltammetry The main contributing factor i n its limited use has been the problem of o b t a ~ k n gsufficient quantities of the compound. By using the technique described above i t is now possible to obtain significant amounts of the material, with the complete preparation including purification taking only about one hour. This time scale coupled to the fact that the apparatus may be reused allows the incorporation of a greater variety of ferrocene chemistry into undergraduate laboratory courses. Literature Cited 1. V@.
0. C.; Peny W. D , J , Chem. Edue 1991.68.607-608.
2. Bozak, R.E. J. Chem. Edur. 1966,43,73.
3. Wade, L . 0 . J Chem Edur 1976,SS.208. 4 . Hew, J. E J Chem. Educ 1966.43.599. 5 . Hsworth, D.T: Liu.T.J.J.Chem. Edue. 1976.53.730. 6. McKone. H.T J. Chem. Edue 1960,S7,380-381. 7. Gi1beit.J.C.;Monti. S. A. J. Chsm. Educ 1973.50.369-370.
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