Beyond Acetylferrocene: The Synthesis and NMR Spectra of a Series

Laboratory Experiment pubs.acs.org/jchemeduc

Beyond Acetylferrocene: The Synthesis and NMR Spectra of a Series of Alkanoylferrocene Derivatives Craig J. Donahue* and Emily R. Donahue Department of Natural Sciences, University of MichiganDearborn, Dearborn, Michigan 48128, United States S Supporting Information *

ABSTRACT: This experiment offers a new twist to a popular undergraduate synthesis laboratorythe conversion of ferrocene to acetylferrocene. The goal of this experiment is to prepare a series of nine alkanoylferrocene complexes that yield more thought-provoking and challenging NMR spectra than that obtained for acetylferrocene. If these complexes are described as alkyl ferrocenyl ketones, the alkyl groups range from methyl (1), ethyl (2), n-propyl (3), isopropyl (4), n-butyl (5), isobutyl (6), tert-butyl (7), n-pentyl (8), to n-heptyl (9). The synthesis and isolation of these crude complexes are achieved by using acid anhydrides or acyl chlorides. In the second week, the crude product was purified by column chromatography and dried. In the third week, 1H and 13C NMR were obtained in CDCl3. These spectra are presented and discussed. KEYWORDS: Upper-Division Undergraduate, Inorganic Chemistry, Laboratory Instruction, Hands-On Learning/Manipulatives, Chromatography, NMR Spectroscopy, Organometallics, Synthesis

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If there is a shortcoming to the traditional ferrocene to acetylferrocene lab experiment, it is that the 1H and 13C NMR spectra for these compounds are very simple and do not challenge students. When confronted with the 1H NMR spectrum of acetylferrocene, students do not have an opportunity to apply their full knowledge of NMR (presented in their second-year organic lecture class) because of its simplicity. In addition, when an entire class prepares acetylferrocene and characterizes it, students do not have the chance to compare and contrast the spectra of a series of related compounds. The laboratory experiment presented here still retains all, or nearly all, of the attractive qualities connected with the synthesis and purification of the acetylferrocene laboratory exercise. This three-week experiment has been performed several times over a four-year span by a total of 34 fourth-year chemistry majors in an inorganic advanced synthesis course. The students worked in pairs, and the preparation, purification, and characterization of these alkanoylferrocene derivatives spanned three 4-h lab periods: (1) synthesis and isolation, (2) column chromatography and purification, and (3) characterization. The students’ primary objective was the acquisition of high quality 1H and 13C NMR spectra of their assigned alkanoylferrocene complex followed by a complete interpretation of these results.

ince the discovery of ferrocene in 1951, thousands of ferrocene derivatives have been prepared, characterized, and adopted for a myriad of applications.1−3 In the context of the undergraduate chemistry curriculum, ferrocene, Fe(η5C5H5)2, is typically discussed in inorganic lecture courses and is often a focus in laboratory courses as well. In the laboratory, one very popular experiment is the conversion of ferrocene to acetylferrocene. This is accomplished either by starting with purchased ferrocene or by preparing ferrocene first4 and then converting it to acetylferrocene. Acetylferrocene is a convenient ferrocene derivative to prepare because ferrocene undergoes electrophilic aromatic substitution reactions one million times faster than benzene.5 This occurs because of the high concentration of electron density in the cyclopentadienyl rings of ferrocene. This experiment also introduces students to column chromatography as a means of separating acetylferrocene from unreacted ferrocene and diacetylferrocenea process made more manageable by the fact that all three species are yellow or orange in color. Further evidence for the popularity of the synthesis of acetylferrocene in undergraduate laboratories is demonstrated by the 20+ articles that have appeared in this Journal dealing with the preparation and purification of acetylferrocene.6−27 The reduction of acetylferrocene to (±)1-ferrocenylethanol has also been reported in this Journal.28 The products of this experiment are a series of alkanoylferrocene species, Fe(η5-C5H5)(η5-C5H4-(CO)-R), where R equals either a straight-chain or branched alkyl group. These nine complexes can also be described as alkyl ferrocenyl ketones where the alkyl groups increase in complexity from methyl (1), ethyl (2), n-propyl (3), isopropyl (4), n-butyl (5), isobutyl (6), tert-butyl (7), n-pentyl (8), to n-heptyl (9). © 2013 American Chemical Society and Division of Chemical Education, Inc.

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EXPERIMENTAL OVERVIEW In the first week, students used one of two synthetic approaches to prepare alkanoylferrocene derivatives. Where the acid anhydride is commercially available, the reaction shown in Published: October 28, 2013 1688

dx.doi.org/10.1021/ed300544n | J. Chem. Educ. 2013, 90, 1688−1691

Journal of Chemical Education

Laboratory Experiment

Scheme 1 was used.29 Many of the acid anhydrides were comparable in cost to acetic anhydride, but some were more

are in the Supporting Information. These are in good agreement with literature values.29−34 All but two of the compounds exhibited first-order behavior. Only for 1hexanoylferrocene (8) and 1-octanoylferrocene (9) were there overlapping methylene signals involving two and four methylene groups, respectively. When the lanthanide shift reagent Eu(fod)3 (fod = 1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl4,6-octanedionate) was employed, the overlapping methylene groups were completely resolved for 1-hexanoylferrocene and partially resolved for 1-octanoylferrocene. Details of the shift reagent studies are provided in the Supporting Information. The richness of the 1H NMR spectra of these complexes is illustrated by the spectrum for 1-pentanoylferrocene (5) (Figure 1). The methyl hydrogens and the three methylene

Scheme 1. Alkanoylferrocenes via Acid Anhydrides

expensive. This approach was used to prepare the entire family of alkanoylferrocene derivatives except for 1-octanoylferrocene (9). The reaction shown in Scheme 2 was used to prepare 1Scheme 2. Alkanoylferrocenes via Acyl Chlorides

octanoylferrocene because octanoic anhydride was not commercially available.30 Additional information about the acid anhydrides and acyl chlorides is provided in the Supporting Information. A detailed description of the procedures related to Schemes 1 and 2 is available in the Supporting Information with a detailed description of the procedures. The NMR spectra were obtained on a 400 MHz NMR spectrometer using CDCl3.

Figure 1. 1H NMR spectra of student-prepared 1-pentanoylferrocene in CDCl3, 1−3 ppm.

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group hydrogens comprising the n-butyl group were clearly resolved. The triplet at ∼1.0 ppm was assigned to the methyl group, the apparent sextet (or more accurately a quartet of overlapping triplets)35 at ∼1.4 ppm is assigned to the methylene group attached to the methyl group, the apparent quintet (or more accurately a triplet of overlapping triplets)35 at ∼1.7 ppm was assigned to the middle methylene group, and the triplet at ∼2.7 ppm was assigned to the methylene group attached to the carbonyl carbon. The more accurate descriptions of the quintet and sextet distinguished between chemical and magnetic equivalency. The presence of the apparent sextet and quintet arose because the hydrogen atoms of the neighboring groups had coupling constants that were approximately equal.35 For comparison purposes, the 13C NMR chemical shift values for the nine alkanoylferrocene complexes were subdivided into three categoriesthe R group carbons, cyclopentadienyl ring carbons, and the carbonyl carbon. These results are presented in the Supporting Information. The R group carbon atoms exhibited chemical shift values ranging from ∼9 to 49 ppm. The carbonyl carbon possessed a chemical shift ranging from 202 to 210 ppm for the nine complexes.

HAZARDS All reagents used in this experiment should be handled exclusively in a fume hood. The anhydrides, boron trifluoride etherate, and octanoyl chloride are flammable, toxic, corrosive, cause severe burns to skin and eyes, and should only be handled with protective clothing including: gloves and eye and face protection. Copious amounts of water should be applied in the event of contact of any anhydride with skin or eyes. Many of the anhydrides have unpleasant odors and should be handled exclusively in a fume hood. Ferrocene is a flammable solid. Zinc oxide is toxic to the environment and should be properly disposed of. Dichloromethane and deuterochloroform are potential carcinogens and irritants to eyes, skin, and should not be inhaled. Ethyl acetate is highly flammable and causes serious eye irritation. Petroleum ether is a highly flammable liquid and maybe fatal if swallowed. Eu(fod)3 is a respiratory, skin, and eye irritant; it is also harmful if swallowed. Acetylferrocene and butyrylferrocene are respiratory, skin, and eye irritants; they are also fatal if swallowed. The associated alkanoylferrocene complexes are assumed to have similar hazards.

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LEARNING OUTCOMES AND ASSESSMENT After completing this experiment, our students were able to successfully interpret the 1H and 13C NMR spectra of their alkanoylferrocene complexes by reporting the relevant chemical shifts, integrations, splitting patterns, and coupling constants. They demonstrated their comprehension of this task by reporting their NMR results in the format employed in the experimental section of an ACS journal such as Inorganic Chemistry, Journal of Organic Chemistry, or Organometallics. They were also required to pool their results and to assemble them into a poster that was presented at the end of the semester at a departmental poster session. This task required

RESULTS AND DISCUSSION Most of the purified n-alkanoylferrocene complexes were red oils, which agreed with the literature.29−31 Acetylferrocene and several of the purified branched-chain alkanoylferrocene complexes were solids at room temperature. Information about the physical state of these complexes is available in the Supporting Information. The characterization of these alkanoylferrocene complexes focused on their 1H and 13C NMR spectra. 1H and 13C NMR spectra for all nine alkanoylferrocene complexes and the 1H NMR data for the R groups of the alkanoylferrocene complexes 1689




(6) Bozak, R. E. Acetylation of Ferrocene: A Chromatography Experiment for Elementary Organic Laboratory. J. Chem. Educ. 1966, 43, 73. (7) Gilbert, J. C.; Monti, S. A. The Separation of Ferrocene, Acetylferrocene, and Diacetylferrocene. A Dry-Column Chromatography Experiment. J. Chem. Educ. 1973, 50, 369−370. (8) Hwa, R.; Weizman, H. Revisiting the Separation of Ferrocene and Acetylferrocene by Adsorption Chromatography: Adding a Third Component. J. Chem. Educ. 2007, 84, 1497−1498. (9) Mosbo, J. A.; Amenta, D. S.; Devore, T. C.; Gallaher, T. N.; Zook, C. M.GC-MS and GC-FTIR Characterization of Products: From Classical Freshman and Sophomore Syntheses. J. Chem. Educ. 1996, 73, 572−575. (10) Heumann, L. V.; Blachard, D. E. Colorful Column Chromatography: A Classroom Demonstration of a Three-Component Separation. J. Chem. Educ. 2008, 85, 524−526. (11) Birdwhistell, K. R.; Nguyen, A.; Ramos, E. J.; Kobelja, R. Acylation of Ferrocene: A Greener Approach. J. Chem. Educ. 2008, 85, 261−262. (12) Wade, L. G., Jr. Illustrative and Inexpensive Column Chromatography Experiment. J. Chem. Educ. 1978, 55, 208. (13) Wilkinson, T. J. Recycling Solvent Mixtures of Ethyl Acetate and Hexanes. J. Chem. Educ. 1998, 75, 1640. (14) Vogel, G. C.; Perry, W. D. Preparation and Characterization of Iron Sandwich Complexes: Celebration of the 40th birthday of Ferrocene. J. Chem. Educ. 1991, 68, 607−608. (15) McKone, H. T. Acylation of ferrocene: Effect of Temperature on Reactivity as Measured by Reverse Phase High Performance Liquid Chromatography. J. Chem. Educ. 1980, 57, 380−381. (16) Bell, W. L.; Edmondson, R. D. Flash ChromatographyThe Simplest Way. J. Chem. Educ. 1986, 63, 361. (17) Haworth, D. T.; Liu, T. Acetylation of Ferrocene. Monitoring a Chemical Reaction by High Pressure Liquid Chromatography. J. Chem. Educ. 1976, 53, 730−731. (18) Winston, A. Design of a Microscale Sublimator. J. Chem. Educ. 1990, 67, 162. (19) Wheeler, J. F.; Wheeler, S. K.; Wright, L. L. Electrochemical Measurements in the Undergraduate Curriculum. J. Chem. Educ. 1997, 74, 72−73. (20) Farrell, J. F.; Pfeil, R.; Caretto, A. A. A chemistry Experience to Enrich High Achievers. J. Chem. Educ. 1988, 65, 150−152. (21) Van Ryswyk, H.; Van Hecke, G. R. Attaining Optimal Conditions: An Advanced Undergraduate Experiment that Introduces Experimental Design and Optimization. J. Chem. Educ. 1991, 68, 878− 882. (22) Baldwin, B. W. Manual Microscale Column Chromatography Pressurization Apparatus. J. Chem. Educ. 2003, 80, 1182. (23) Bohen, J. M.; Joullié, M. M.; Kaplan, F. A.; Loev, B. “Drycolumn” Chromatography. A New Technique for the Undergraduate Laboratory. J. Chem. Educ. 1973, 50, 367−368. (24) Shusterman, A. J.; McDougal, P. G.; Glasfeld, A. Dry-Column Flash Chromatography. J. Chem. Educ. 1997, 74, 1222−1223. (25) Newirth, T. L.; Srouji, N. Acetylation of Ferrocene: A Study of the Friedel-Crafts Acylation Mechanism as Measured by HPLC Using an Internal Standard. J. Chem. Educ. 1995, 72, 454−456. (26) Davis, J.; Vaughan, D. H.; Cardosi, M. F. An Enhanced Chromatographic Technique for the Preparative Scale Purification of Acetyl Ferrocene. J. Chem. Educ. 1995, 72, 266−267. (27) Herz, J. E. Optimizing Experimental Conditions: The Use of TLC to Follow the Course of a Reaction. J. Chem. Educ. 1966, 43, 599. (28) Hamilton, D. E. Reduction of Acetylferrocene with Lithium Aluminum Hydride and Resolution of the Enantiomers with a Chiral HPLC Column: An Experiment for the Advanced Undergraduate Laboratory. J. Chem. Educ. 1991, 68, A143−A144. (29) Jary, W. G.; Mahler, W. G.; Purkahofer, T.; Bamgartner, J. A Convenient Synthesis of E-alkenylferrocenes. J. Organomet. Chem. 2001, 629, 208−212.

our students to inspect the entire set of data, to identify similarities in the data (e.g., in chemical shift values and coupling constants between complexes) and to describe the splitting pattern of the R group hydrogens in the 1H NMR spectra. In addition, students had to formulate explanations (e.g., for the inability to resolve the splitting in the methylene groups in the 1H NMR spectra of 1-hexanoylferrocene and 1octanoylferrocene), to appraise the overall success of the project, and to propose solutions to obstacles or undesirable outcomes (e.g., the use of a lanthanide shift reagent to resolve overlapping peaks in the 1H NMR spectra).

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SUMMARY Students responded positively to the challenge of preparing, purifying, and characterizing, by 1H and 13C NMR spectroscopy, the nine alkanoylferrocene derivatives. They were surprised by the splitting observed in the 1H NMR spectra for the R groups of most of the complexes and enjoyed the opportunity to explain how the splitting arises. Challenged to compare and contrast the 1H and 13C NMR spectra of the entire set of complexes, students realized that the spectra of the complexes were very similar aside from the signals due to the R groups. They also appreciated that, as the R group changed in size, eventually first-order splitting in the 1H NMR spectra was no longer observed.

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ASSOCIATED CONTENT

S Supporting Information *

Alternative names for alkanoylferrocene complexes; properties and CAS numbers of acid anhydrides and acyl chlorides; melting points, summary of 1H NMR, 13C NMR, IR, and mass spectrum results for alkanoylferrocene complexes; 1H NMR and 13C NMR spectra; detailed student handout; instructor notes. This material is available via the Internet at http://pubs. acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS C.J.D. thanks the Office of the Dean, The College of Arts, Sciences, and Letters, University of MichiganDearborn for financial support for this project through an Associate Professor Career Grant. The authors thank the reviewers for helpful suggestions.

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REFERENCES

(1) Ferrocene: Ligands, Materials, and Biomolecules; Štĕpnička, P., Ed.; John Wiley & Sons, Ltd: Chichester, U.K., 2008. (2) Chiral Ferrocenes in Asymmetric Catalysis; Dai, L., Xue-Long, H., Eds.; Wiley-VCH: Weinheim, 2010. (3) Ferrocenes: Compounds, Properties and Applications (Chemical Engineering Methods and Technology); Phillips, E. S., Ed.; Nova Science Publishers, Inc.: New York, 2011. (4) Jolly, W. L. The Synthesis and Characterization of Inorganic Compounds’ Prentice Hall, Inc.: Englewood Cliffs, NJ, 1970; p 484. (5) Spessard, G. O.; Miessler, G. L. Organometallic Chemistry; Oxford University Press, Inc.: Oxford, 2010; Chapter 5. 1690




(30) Wang, R.; Hong, X.; Shan, Z. A Novel, Convenient Access to Acylferrocenes: Acylation of Ferrocene with Acyl Chlorides in the Presence of Zinc Oxide. Tetrahedron Lett. 2008, 49, 636−639. (31) Hu, R.; Lei, M.; Xiong, H.; Mu, X.; Wang, Y.; Yin, X. Highly Selective Acylation of Ferrocene using Microfluidic Chip Reactor. Tetrahedron Lett. 2008, 49, 387−389. (32) Stark, A.; MacLean, B. L.; Singer, R. D. 1-Ethyl-3methylimidazolium Halogenoaluminate Ionic Liquids as Solvents for Friedel−Crafts Acylation Reactions of Ferrocene. J. Chem. Soc., Dalton Trans. 1999, 63−66. (33) Vukićević, R. D.; Ratković, Z. R.; Vukićević, M. D.; Konstantinović, S. K. A Novel Method for Preparation of Acylferrocenes. Tetrahedron Lett. 1998, 39, 5837−5838. (34) Ranson, R. J.; Roberts, R. M. G. 13C Chemical Shifts and Carbonyl Stretching Frequencies as Structural Probes for Ferrocenyl Ketones. J. Organomet. Chem. 1984, 260, 307−317. (35) Hoye, T. R.; Hanson, P. R.; Vyvyan, J. R. A Practical Guide to First-Order Multiplet Analysis in 1H NMR Spectroscopy. J. Org. Chem. 1994, 59, 4096−4103.

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Beyond Acetylferrocene: The Synthesis and NMR Spectra of a Series

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