Chemical Education Today edited by
NSF Highlights
Susan H. Hixson
Projects Supported by the NSF Division of Undergraduate Education
National Science Foundation Arlington, VA 22230
Richard F. Jones Sinclair Community College Dayton, OH 45402-1460
Microscale Syntheses, Reactions, and 1H NMR Spectroscopic Investigations of Square Planar Macrocyclic Tetraamido-N Cu(III) Complexes Relevant to Green Chemistry
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by Erich S. Uffelman,* Jonathan R. Doherty, Carl Schulze, Amy L. Burke, Kristen R. Bonnema, Tanya T. Watson, and Daniel W. Lee, III
Over the past six years, we have developed a series of new NMR experiments across our undergraduate curriculum based on the acquisition of a 400 MHz multinuclear FT NMR with the assistance of the NSF-ILI program (1). Our two-credit inorganic synthesis and spectroscopy laboratory, Chem 252, is geared for junior and senior chemistry majors. It has been created as a problem-based learning environment that integrates lab and lecture and builds on foundations laid in lower-level chemistry courses. Chem 252 is described to students as “a lab of patents,” since all of the experiments involve recently patented ligands, complexes, or processes (1b, 1d, 2). We present here the microscale preparation, characterization, and reactivity of a square planar Cu(III) complex that has grown out of our program to introduce experiments of relevance to green chemistry into the undergraduate curriculum. Now that there are two wellestablished two-step routes in the literature to the macrocyclic tetraamide ligands described here (3), and given that these ligands are commercially available (4), we believe that this lab and an analogous one involving square planar Co(III) (1d) are ready for dissemination, especially since these experiments only require 6 mg of macrocycle per student. The class of macrocyclic ligands shown below (Figure 1) has attracted considerable attention because it is remarkably robust to oxidative and hydrolytic decomposition and thus: (i) makes it possible to isolate and study unusually high oxidation states of first row transition metals (5), (ii) permits unusual coordination geometries of the first row transition metals to be studied (6), (iii) is crucial to new industrially viable catalytic processes in which the relevant macrocyclic iron complexes activate hydrogen peroxide (7). Cu(III)
a O X
b
R R
O
NH HN
R'
X
N
X
NH HN
R
Cl
N
R' R'
N
N
O
RR
O
O O
RR
2ⴚ O
Fe
R' X
R
O
Figure 1. (a) Tetraamide macrocycles protected against oxidative decomposition. When tetradeprotonated, these tetraanionic macrocycles are powerful sigma electron donors to metal ions. (b) This family of iron complexes serves as catalytic activators of hydrogen peroxide for industrially important, environmentally friendly oxidations (7).
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complexes were the subject of considerable interest because of galactose oxidase (8) and continue to be of interest due to the intriguing reactivity of recently discovered complexes (9). The set of experiments and spectra described below takes two or three, four-hour lab periods to complete and involves the transformations shown in Figure 2. These experiments illustrate the remarkable redox and aqueous acid–base stability that make the macrocycles so useful when applied to iron-based green oxidations, and the experiments introduce students to classic aspects of square planar d8 transition metal chemistry via the novel example of Cu(III). Procedure H41 (3, 4) (6–7.5 mg) is weighed into a 3 mL 14/10 conical vial on an analytical balance. Anhydrous Cu(OAc)2 (5 mg) is quickly added into the conical vial. A conical ministir bar is added to the vial, followed by acetonitrile (0.6 mL) and ethyldiisopropylamine (4 drops). A 14/10 straight tube is attached to the conical vial, and the reaction mixture is heated at gentle reflux (50 min) with stirring. The mixture changes from a blue suspension to a brown solution as the reaction proceeds. When the reaction is finished, TLC (silica gel/acetone) reveals a brown spot near the solvent front and copper byproducts at the origin. The solution is evaporated to dryness under vacuum and the residue is dissolved in acetone (0.6 mL) and filtered through a 1.5 cm silica gel pad in a glass pipet. Another 1–2 mL of acetone is used to flush the brown product through the column, being careful to leave the byproducts stuck on the silica gel. The acetone solution is evaporated to dryness and the residue is washed with hexanes (2 × 1 mL). The brown solid is dried briefly under vacuum, dissolved in CDCl3 (0.8 mL), and filtered into an NMR tube. A 1H NMR spectrum is obtained. The CDCl3 product solution is returned to a conical vial, diluted with CH2Cl2 (0.5 mL), and treated with aqueous NaOH (1 M, 1 mL). The brown product extracts into the aqueous layer. The halocarbon layer is removed by pipet, keeping the aqueous solution in the conical vial. The aqueous solution is washed with CH2Cl2 (2 × 1 mL) using a pipet to discard the washes. To aqueous Na[Cu(1)] is added a few drops of concentrated aqueous tetrabutylammonium chloride ([Bu4N]Cl). The brown [Bu4N][Cu(1)] precipitate is centrifuged, and the supernatant is carefully discarded. The [Bu4N][Cu(1)] is washed and centrifuged twice more with
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water (2 × 1 mL). The [Bu4N][Cu(1)] is dissolved in CH2Cl2 (1 mL) and dried with anhydrous MgSO4. The solution is evaporated to dryness under vacuum. [Bu4N][Cu(1)] is dissolved in CDCl3 (0.8 mL), and the resulting solution is filtered into an NMR tube. A 1H NMR spectrum is obtained, along with UV-vis and FTIR spectra, if desired. The CDCl3 solution of [Bu4N][Cu(1)] is transferred to another small, screw-cap vial. Br2 (half a drop) is added to CDCl3 (4–6 drops) in a small screw-cap vial. Less than a full drop of the Br2/CDCl3 solution is added to the CDCl3 solution of [Bu4N][Cu(1)]. If precipitation occurs, dilute aqueous NaOH (2 drops) is added to the vial, which is then shaken until the precipitate goes back into solution. The CDCl3 solution is dried over MgSO4 (if it was treated with aqueous base) and filtered into an NMR tube for a 1H NMR spectrum.
the formation constants for transition metal complexes of ammonia versus hindered trialkylamines. 3. Redox. Because Cu(OAc)2 contains Cu(II) and [Cu(1)]⫺ contains Cu(III), the students are asked why a Cu(III) complex is not chosen as a starting material (it is a rare oxidation state for copper), and they are asked what oxidizes the copper during the reaction (O2). These questions make the students consider “reagents” they might have in a reaction that are not listed in the procedure. The students are also asked to ponder the fate of the superoxide byproduct. Students explain, using the background reading (5f ), the design features of the macrocycle that protect it from decomposition. 4. Le Châtelier’s principle. Connected with the Brønsted acid– base and redox ideas above, the students explain how the irreversible oxidation of the metallated macrocycle from Cu(II) to Cu(III) pulls the reaction to completion.
Problem-Based Learning Environment
5. Nonaqueous chemistry. Although the copper insertion does not require anhydrous solvents or drying tubes, it does not work in aqueous solution. Students consider the fate of anhydrous Cu(OAc)2 if it were to be dissolved in water or wet organic solvents in the presence of hydroxide (flocculent blue Cu(OH)2 precipitates form).
In addition to the lab manuals, the students have access to a microscale laboratory textbook for general procedures (10). Three papers (11) from the literature on green chemistry and high-valent transition metal chemistry are also given to students as background reading for these experiments. The nine points below are the key focus of student–student and student–professor discussions and questions during the lab lectures, and they are also an integral component of the student lab write-ups.
6. Solubility product constants. Students explain the different aqueous and non-aqueous solubilities of the different salts employed and formed in these experiments based on the “organic” or “inorganic” character of the individual ions. Students estimate the value of Ksp that would lead to 90% versus 99% versus 99.9% precipitation of the [Bu4N][Cu(1)] salt.
1. Brønsted acid–base chemistry. In the lab manual and pre-lab lecture, students are asked to consider that the pKa of an organic amide is 18–22, while the pKa of a protonated tertiary amine is 10–11. Students demonstrate with rough calculations that very little H41 is deprotonated by diisopropylethylamine and are asked how it can be efficacious in the metallation reaction. Students demonstrate with a rough calculation that hydroxide is sufficiently basic to deprotonate [Is2EtNH]⫹.
7. Periodic trends. Since the Cu(III) complex is d8 square planar, students explain why Br2 brominates the aromatic ring of the macrocycle, rather than doing an oxidative addition at the metal, as Ir(I) or Pt(II) d8 square planar complexes might. 8. Organic reactivity. Students are reminded that benzene requires a catalyst to be brominated by Br2 and that phenol does not need a catalyst to be brominated. They are asked to explain why [Bu4N][Cu(1)] needs no catalyst for aromatic ring bromination.
2. Sterics. Students consider in pre-lab lecture that if diisopropylethylamine is effective in the metallation reaction, why not use NH3? Students are led through a discussion of
O
O
O
O NH HN
Cu(OAc)2 MeCN
NH HN
iPr2 EtN ∆, O2
N N Cu N N
ⴙ [iPr2EtNH]
O
O
*NMR O
O
Figure 2. Chemical transformations in these copper experiments.
ⴚ
NaOH
H41 ⴚ
O
Na[Cu(1)] [Bu4N][Cl]
O
ⴙ
N
[Bu4N] *NMR
N
Br2
Cu N
Br1-4
N
[Bu4N][Cu(1)] *NMR
O O
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NSF Highlights 9. Spectroscopy. The students are led through the ligand field diagram for d8 square planar complexes and are asked to explain the diamagnetic NMR spectra obtained for the Cu(III) complexes. Most students initially forget they are not preparing a neutral complex and are thus surprised and initially nonplused by the appearance of the protonated trialkylammonium cation signals in the NMR. Also, because students use different amounts of complex and Br2 in their bromination experiment, they obtain different levels of bromination of the aromatic ring (one student running this experiment actually succeeded in brominating all four available ring positions, so that the aromatic region of her spectrum disappeared). Students thus get different mixtures of compounds with different spectra. This causes many students to ask, “What did I do wrong?” They are told they did nothing wrong—they need to determine what they actually did.
The FTIR spectroscopy can be omitted, but if performed it illustrates that the amide carbonyl peaks [Bu4N][Cu(1)] (1631, 1584, 1571, 1562 cm–1) are at lower frequencies compared to H41 (1702, 1680, 1652, 1635 cm–1), as expected based on amide resonance structures consistent with more electron density at the carbonyl oxygen in the anionic complex versus the neutral ligand. The UV-vis spectroscopy can be omitted, but if it is done, the molar extinction coefficient of the visible band (>1000 M⫺1cm⫺1, λmax ⫽ 422 nm) indicates that the students are seeing a ligand to metal charge transfer transition. Assessment and Conclusions Students record their procedures, observations, and calculations in a lab notebook, as well as their answers to prelab and post-lab questions concerning the nine points discussed above. Students are also responsible for this material during pre-lab lectures and on their end of term cumulative lab final exam. The synthesis and spectroscopy of these complexes is experimentally reliable, making this experiment an excellent introduction to microscale work. Students appreciate the experience with a macrocyclic ligand relevant to green chemistry. After the lab is concluded, students enjoy seeing how much of their chemistry background is relevant to understanding this work. The laboratory final exam at the end of the term indicates that students generally absorb most of the key points of this laboratory experience. Hazards Br2 is a caustic, volatile liquid. Standard precautions involving organic solvents and glassware under vacuum should be taken. Students are given a list of possible health hazards associated with strong magnetic fields (e.g., pacemakers, metal implants, etc.) and told to inform the instructor if they should be kept a safe distance from the NMR magnet. W
Supplemental Material
Full documentation of these materials is available in this issue of JCE Online. 184
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Acknowledgments We thank the National Science Foundation ILI program (Grant No. DUE-9650033) for support in purchasing a JEOL Eclipse+ 400 MHz spectrometer. We thank Charles Steinmetz for facilitating a Hewlett-Packard University Equipment Gift of a diode array UV-vis spectrophotometer (HP 8453 UV–vis system, gift number 37353). ESU thanks the Washington and Lee University Glenn Grant program for summer support. ESU also thanks the Washington and Lee Class of 1965 for two Excellence in Teaching Awards that supported development of new NMR experiments across the Chemistry Department curriculum. Related work that supported these experiments was funded by the Research Corp. (Grant No. CC3870), and the donors of the Petroleum Research Fund, administered by the American Chemical Society (Grant No. 29495-GB3). JRD, CS, ALB, KB, TTW, and DWL thank Washington and Lee for Summer Research Student Fellowships. Literature Cited 1. (a) France, M. B.; Alty, L. T.; Earl, T. M. J. Chem. Educ. 1999, 76, 659. (b) France, M. B.; Uffelman, E. S. J. Chem. Educ. 1999, 76, 661. (c) Uffelman, E. S.; Cox, E. H.; Davis, C. M.; Goehring, J. B.; Lorig, T. An NMR-Smell Module for the First Semester General Chemistry Laboratory. J. Chem. Educ. 2003, 80, 1368–1372. (d) Uffelman, E. S.; Doherty, J. R.; Schulze, C.; Burke, A. L.; Bonnema, K.; Watson, T. T.; Lee, D.W., III. Microscale Syntheses, Reactions, and 1H-NMR Spectroscopic Investigations of Square Planar Macrocyclic Tetraamido-N Co(III) Complexes Relevant to Green Chemistry. J. Chem. Educ., in press. (e) Alty, L. T. Terpene Unknowns Identified Using IR, 1H NMR, 13C NMR, DEPT, COSY and HETCOR. J. Chem. Educ., submitted for publication. 2. (a) Szafran, Z.; Pike, R. M.; Singh, M. M. Microscale Inorganic Chemistry: A Comprehensive Laboratory Experience; Wiley: New York, 1991; pp 176–180. (b) Szafran, Z.; Pike, R. M.; Singh, M. M. Microscale Inorganic Chemistry: A Comprehensive Laboratory Experience; Wiley: New York, 1991; pp 337– 341. (c) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063–7064. 3. The original four-step synthesis may be found in (a) and (b), while the two different two-step syntheses may be found in (c), (d), and (e). (a) Uffelman, E. S. Macrocyclic Tetraamido-N Ligands That Stabilize High-Valent Complexes of Chromium, Manganese, Iron, Cobalt, Nickel, and Copper. Ph.D. Dissertation, California Institute of Technology, Pasadena, CA, 1991. (b) Collins, T. J.; Powell, R. D.; Slebodnick, C.; Uffelman, E. S. J. Am. Chem. Soc. 1991, 113 8419–8425. (c) Gordon-Wylie, S. W. High-Valent Manganese and Cobalt Complexes of Oxidatively Robust N and O Donor Ligands. Ph.D. Dissertation, Carnegie Mellon University, Pittsburgh, PA, 1995. (d) Collins, T. J.; Gordon-Wylie, S. W.; Woomer, C. G.; Horwitz, C. P.; Uffelman, E. S. Homogeneous Oxidation Catalysis Using Metal Complexes. PCT Int. Appl., 1998, 62 pp. (e) Rorrer, L. C.; Hopkins, S. D.; Connors, M. K.; Lee, D. W., III; Smith, M. V.; Rhodes, H. J.; Uffelman, E. S.
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Organic Letters 1999, 1, 1157–1159. 4. Information on the production of the macrocycles is updated at this Web site http://www.chem.cmu.edu/groups/collins/(accessed Dec 2003). To obtain samples of macrocycle for the laboratory experiment discussed in this paper, use the information found at the Web site and contact Terrence J. Collins or Colin Horwitz for pricing and quantities. These macrocycles can also be synthesized by methods published in the Supplemental MaterialW accompanying this paper. 5. (a) Collins, T. J.; Powell, R. D.; Slebodnick, C.; Uffelman, E. S. J. Am. Chem. Soc. 1990, 112, 899–901. (b) Collins, T. J.; Kostka, K. L.; Münck, E.; Uffelman, E. S. J. Am. Chem. Soc. 1990, 112, 5637–5639. (c) Collins, T. J.; Nichols, T. R.; Uffelman, E. S. J. Am. Chem. Soc. 1991, 113, 4708–4709. (d) Collins, T. J.; Slebodnick, C.; Uffelman, E. S. Inorg. Chem. 1990, 29, 3432–3436. (e) Collins, T. J.; Kostka, K. L.; Uffelman, E. S.; Weinberger, T. Inorg. Chem. 1991, 30, 4204– 4210. (f ) Collins, T. J. Acc. Chem. Res. 1994, 27, 279–285. (g) Bartos, M. J.; Gordon-Wylie, S. W.; Fow, B. G.; Wright, L. J.; Weintraub, S. T.; Kauffmann, K. E.; Münck, E.; Kostka, K. L.; Uffelman, E. S.; Rickard, C. E. F.; Noon, K. R.; Collins, T. J. Coord. Chem. Rev. 1998, 174, 361–390. (h) Miller, C. G.; Gordon-Wylie, S. W.; Horwitz, C. P.; Strazisar, S. A.; Peraino, D. K.; Clark, G. R.; Weintraub, S. T.; Collins, T. J. J. Am. Chem. Soc. 1998, 120, 11540–11541. (i) Horwitz, C. P.; Fooksman, D. R.; Vuocolo, L. D.; Gordon-Wylie, S. W.; Cox, N. J.; Collins, T. J. J. Am. Chem. Soc. 1998, 120, 4867– 4868. 6. Collins, T. J.; Uffelman, E. S. Angew. Chem. Int. Ed. Engl. 1989, 28, 1509–1511. 7. (a) Gupta, S. S.; Stadler, M.; Noser, C. A.; Ghosh, A.; Steinhoff, B. A.; Lenoir, D.; Horwitz, C. P.; Schramm, K. W.; Collins, T. J. Science 2002, 296, 326–328. (b) Collins, T. J.
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8.
9.
10.
11.
Acc. Chem. Res. 2002, 35, 782–790. (c) Patterson, R. E.; Gordon-Wylie, S. W.; Woomer, C. G.; Norman, R. E.; Weintraub, S. T.; Horwitz, C. P.; Collins, T. J. Inorg. Chem. 1998, 37, 4748–4750. (d) Collins, T. J.; Gordon-Wylie, S. W.; Bartos, M. J.; Horwitz, C. P.; Woomer, C. G.; Williams, S. A.; Patterson, R. E.; Vuocolo, L. D.; Paterno, S. A.; Strazisar, S. A.; Peraino, D. K.; Dudash, C. A. “The design of green oxidants,” in Green Chemistry: Frontiers in Benign Chemical Syntheses and Processes; Anastas, P. T., Williamson, T. C., Eds.; Oxford University Press: Oxford, 1998; pp 46–71. Prior to the detailed characterization of the Cu(II) tyrosine radical, it was postulated that galactose oxidase might contain Cu(III). See McPherson, M. J.; Parsons, M. R.; Spooner, R. K.; Wil-mot, C. M. in Handbook of Metallo-proteins; Messerschmidt, A.; Huber, R.; Poulos, T.; Wieghardt, K.; Wiley: New York, 2001; pp 1272–1283. Ribas, X.; Jackson, D. A.; Donnadieu, B.; Mahia, J.; Parella, T.; Xifra, R.; Hedman, B.; Hodgson, K. O.; Llobet, A.; Stack, T. D. P. Angew. Chem., Int. Ed. Engl. 2002, 41, 2991–2994 and references therein. Szafran, Z.; Pike, R. M.; Singh, M. M. Microscale Inorganic Chemistry: A Comprehensive Laboratory Experience; Wiley: New York, 1991. We currently use references 5f, 7a, and 7b. In previous years we have used reference 5f and 7d.
In the NSF Highlights column, recipients of NSF CCLI grants share their project plans and preliminary findings. Erich S. Uffelman is in the Department of Chemistry, Washington and Lee University, Lexington, VA 24450;
[email protected]. Jonathan R. Doherty, Carl Schulze, Amy L. Burke, Kristen R. Bonnema, Tanya T. Watson, and Daniel W. Lee, III are former students who participated in this project.
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