Reduction of Acetylferrocene with Lithium Aluminum Hydride and ~esolutionof the Enantiomers with a Chiral HPLC Column An Experiment for the Advanced Undergraduate Laboratory Dorothy E. Hamilton Smith College, Northampton, MA 01 063 Procedures for the synthesis of femcene and its acetylation with acetic anhydride are reported in many laboratory texts. These syntheses can be extended to include the preparation of (?)I-ferrocenylethanol (see figure). Described herein is a procedure for the reduction of ( i l l -
femcenylethanol using lithium aluminum hydride that is a modificationof the procedure reported in 1955by Arimoto andHaven ( I ) .Synthesis ofthe crude product can be camed out by students in one 3-h lab period. The procedure described in this paper introduces students to the use of syringes for transferring reagents and to carrying out reactions under a nitrogen atmosphere. The purified product can be analyzed in many ways, as time and resources permit. This experiment has been used to introduce students to the Gmelin Handbook oflnorganic Chemistry, since they must compare melting points and spectral results to those reported in the literature for ( i l l ferrocenylethanol as well as to spectral data for ferrocene and acetylferrocene. Spectral data ('H NMR, 'W NMR, UV-vis, and IR) and references for (?)I-ferrocenylethanol are given in the Experimental section. Another interesting property of (f)l-ferrocenylethanol that may he studied is its electrochemical behavior. Cyclic voltammetry may be performed on ferrocene, acetylferrocene, and (i)l-ferrocenylethanol. Ferrocene and (f)l-ferrocenylethanol are reversible systems, while acetylferrocene is pseudo-reversible. In each case the iron is cycling between the +2 and +3 oxidation states. The electron-withdrawing carhonyl in acetylfemcene has a pronounced effect on the redox couple, as compared to that of ferrocene or ( i l l - f e e n y l e t h a n o l (see the table). Separation of the enantiomers of (f)l-ferrocenylethanol is possible by liquid chromatography with a P-cyclodextrin section of the Journal called The Modern Student Laboratory, which will periodically feature laboratory experiments that use the Instruments and techniques students will be required
Redox Potentials for Ferrocene and Derivatives Compound
fin VS.SCE
(mv) Ferrocene Acetylferrocene 1-Ferrocenylethanol
column (2). An inclusiou complex is formed between 1ferrocenylethanol and the cyclodextrin cavity. The hydrogen-bonding interaction between hydroxyl groups at the "mouth" of the cyclodextrin cavity and the hydroxyl group of the alcohol differs for each enantiomer, which leads to different retention times for the enantiomers. If a more detailed discussion of this techniques is desired, the formation of inclusion complexes by cyclodextrins and the use of these materials in liquid chromatography for the separation of optical isomers h a s been reviewed by S.Keulemansova (3). Experimental
Caution: Lithium aluminum hydride is flammable and reacts vigorously with water. Students should be instructed to wear safety glasses and gloves a t all times in a chemistry laboratory, hut especially when handling the lithium aluminum hydride solution. Students should be su~ervised when the; are transferring the lithium a~uminum'h~dride solution. Students should also be reminded of the dancers of heating ether solutions, since ether is flammable a n d forms peroxides upon prolonged storage. Equip a 100-mL, two-necked, round-bottomed flask with a condenser and a pressure-equalizing addition funnel (10 mL). Using a T-connector, attach a nitrogen line and bubbler to the top of the condenser, and flush the system with nitrogen. Add a magnetic stir bar, anhydrous ether (25mL), and acetylferrocene (1.00 g, 4.38 mmol; available from Aldrich) to the flask. Attach a septum stopper to the top of the addition funnel. Heat the system to a slow reflux. Usinga syringe, transfer 2.0 mLof 1M lithium aluminum hydride solution in diethyl ether (Aldrich) to the addition funnel. While the acetylfemcene solution is being stirred add the lithium aluminum hydride solution dropwise. Reflux the mixture for 15 min after the addition is complete, then discontinue heating. (Continued on page A1 44) Volume 68 Number 6 June 1991
A143
The Modern Student laboratory: Chromatography Excess lithium aluminum hydride can be destroyed with ethyl acctate. TransVera smelian~ount(0.5 m ~ i s s u f f i c i e n t , ofethyl acctate to theaddition funnel. Add thccthyl acetate dropwisr to the reachon mixture unril there is no widencs of reaction, that is, there is no bubbling upon addition. Cool the solution in ice water, then Hdd a n aqueous solution of ammonium chloride (1.1E in 10 mL water). Stir the mixture in a n ice bath for 15 &, and gravityfilter to remove a white solid (lithium and aluminum bvproducts). Wash the solid with a small amount of ether. fiansfer the filtrate and ether washings to a small separatory funnel and remove the aqueous phase. Wash the organic phase with water (2 x 5 mL), then dry with sodium sulfate. Remove the drying agent by gravity filtration, and wash the sodium sulfate with a small amount of ether. Remove to obtain the solidvellow the ether with a rotarv eva~orator alcohol. Recrystallize"the iroduct from a n 80120 vlv A t u r e of uetroleum etherldiethvl ether to obtain vellow needles. h e yield of crude pro&ct is about 90%~-whilea yield of about 70% is obtained after recrystallization. The melting point of 1-fermcenylethanol is reported as 78-79 "C (4).The melting point of the recrystallized product will be close to this, while the melting point of the crude product is generally 5-10 "C lower. Spectral data are a s follows. 'H NMR (CDCld 6 4.52 (m, lH), 4.25 (m, 4H), 4.21 (s, 5H), 1.87 (d, J = 4.6 Hz, l H , or bmad s), and 1.44 (d, J = 6.4 Hz, 3H), in agreement with reported values (5).13CNMR (benzene-ds) 6 95.5,68.0, and 66.4 (substituted cyclopentadiene ring), 6 68.6 (unsubstituted cyclopen&di&e ring), 65.6 (hydroxyl-bearing carbon), and 24.3 (methyl), similar to values reported by
A144
Journal of Chemical Education
Williams e t al. (6).UV-vis (ethanol, 300-650 nm) 436.4 nm (E 971, 324.5 nm (E 581, similar to reported values (7). IR (CHCld showed OH stretches between 3500 and 3600 cm-I, which have been assigned to "free" OH (8,9),n-bonded OH (81, and Fe-bonded OH (9);3100, 3000, 2980, 2940, 2900, 1380,1260,1110,1000,830 m-'. Cyclic voltammetry was performed using a BAS CV-1B potentiostat with a n XY recorder on 4 mM solutions of ferrocene, acetylated fermcene, and (It)l-ferrocenylethanol in dichloromethane containine 0.2 M tetraethvlarnmonium tetrafluoroborate. A platinum-working eledldde, platinum auxiliary electrode, and SCE reference electrode were used. The initial potential was set a t 0 V, and scanlimits of 0 and 1.25 V were used. The scan rate was 100 mVls. Liquid chromatography with a P-cyclodextrin column was performed using a slight modification of the procedure reported by Armstrong et al. (2). A mobile phase of 75% methanol/25% water was used with a flow rate of 0.8 mumin. The column (250 mm x 4.6 mm) was obtained from Advanced Separation Technologies Inc., Whippany, NJ, (201) 428-9080. Literature Cited 1.Anmob, F. S.:H8ven.A. C., Jr. J Am. Ckern. Sm. 1955.77.6295-6297, 2 h s t r a n g . D. W.;DeMond,W.; Czech,B. P h o l Cham. 1985,57,481-484. 3. S-Keulemsnsova, E. J. Chmmologr, Chmrnologr. Re". 1982,251, 17. 4. Hauser, C. R.; Lindsay, J. K. J. Org. Chom. 1957.22, 906908. 5. Horspool, W. H.; Sutherlsnd, R. G.; Sutton, J. R. Can. J. Cham. l B 9 , 47,30853088. 6 . Williams. G. H.; Traficante, D. D.; Seyferth. D. J. O~gonometChem. 1978, 60,
