Chemical Education Today edited by Susan H. Hixson
NSF Highlights Projects Supported by the NSF Division of Undergraduate Education
Organic Chemistry Course Development in a Forensic Science Program: Use of FT-NMR
National Science Foundation Arlington, VA 22230
Richard F. Jones Sinclair Community College Dayton, OH 45402-1460
by Ronald Callahan, Lawrence Kobilinsky and Robert Rothchild*
John Jay College has been able to acquire a 7.0-tesla Fourier transform NMR (FT-NMR) spectrometer with a variable-temperature multinuclear (1H, 13C, 19F, 31P) probe, aided by awards from the NSF–ILI program. The College is a special-purpose senior college within the City University of New York (CUNY) with a mission in the broad areas of criminal justice and public service; the only formal science programs offered here lead to B.S. and M.S. degrees in forensic science (with tracks in criminalistics and in toxicology). The program, in many respects, resembles that of an analytical chemistry major, with a heavy emphasis on chemistry, including a two- semester organic chemistry course. The Science Department also has a 60-MHz continuous-wave proton NMR spectrometer, ca. 18 years old, obtained through an early NSF–ISEP award. The recent acquisition of a modern, superconducting FT-NMR instrument has made an enormous impact on the forensic science major, but we will focus here on applications within the organic chemistry course and on related undergraduate and graduate research opportunities. For some years, one of us had been involved in NMR studies using lanthanide shift reagents (LSR). It was the use of LSR applied to a Diels–Alder adduct of phencyclone with norbornadiene (working with our old 60-MHz NMR) that allowed us to recognize the unusual hindered rotation of the unsubstituted bridgehead phenyl groups (1). Subsequent studies with a medium-field NMR (200-MHz proton, 50- MHz carbon-13) allowed us to confirm and elucidate aspects of these adducts (2). But only in the last few years with our current FT-NMR have we really been able to extend these studies into a major 7–8 week “special project” in the secondsemester organic chemistry course (3). Because student interest and motivation have dramatically increased, students have continued work on these projects during the summers and the following semesters. The project has allowed undergraduates and graduates to participate in research that has earned them co-authorships on published or presented research papers (4 –13). The students can synthesize phencyclone, 1, as an example of a base-promoted aldol condensation from 9,10phenanthrenequinone and 1,3-diphenyl-2-propanone (14 – 16). This satisfying experiment gives a dramatic color change as the intense green-black phencyclone forms, and it allows a logical discussion of the effects of increasing conjugation upon the wavelengths of absorption maxima in the UV–vis spectrum. This synthesis is easy enough to be done in the first semester. In the second term of the organic chemistry lab, students can use their phencyclone for reactions with di*Corresponding author.
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verse Diels–Alder dienophiles, following reaction progress qualitatively via the discharge of the phencyclone color (17). We have found that N-substituted maleimides constitute a broad class of dienophiles that are especially useful for this undergraduate special project. The reaction rates of the maleimides with phencyclone are conveniently fast. Many different maleimides can be prepared so that every student in a lab section has his or her own unique target compounds. Some maleimides are commercially available, but most can usually be obtained in two different ways. For example, reaction of a primary amine with equimolar maleic anhydride gives the N-substituted maleamic acid in high yield (typically greater than 80% for crude material and almost always crystalline or semisolid) which can undergo cyclodehydration with acetic anhydride and anhydrous sodium acetate (by heating in a boiling water bath). Although the resulting maleimides are typically impure oils, the crude materials can be directly used with phencyclone since the desired adducts are highly crystalline and usually isolable from the reaction mixture (3). An alternative method for making some maleimides—by refluxing the maleamic acid in a mixture of acetone, acetic anhydride, and triethylamine—may also be used (18). Most of the target compounds and precursors for this special project have been prepared as microscale reactions. See Scheme 1. The Diels–Alder adducts, 2, are thoroughly characterized by one- and two-dimensional (1-D and 2-D) NMR. This provides a superb opportunity to introduce modern NMR methods (COSY, HETCOR) for homonuclear and heteronuclear correlation spectroscopy. Without dealing with the theoretical bases for these experiments, students learn to appreciate the enormous amount of information provided by the NMR spectra, and the directness of much of the interpretations and assignments. The phencyclone adducts have been a rich group of compounds to examine since: a. b.
c.
d.
adequate dispersion is achieved (at 300 MHz for proton, 75 MHz for carbon-13) to separate most signals; incontrovertible evidence for hindered rotation of the unsubstituted bridgehead phenyls is clearly demonstrated by proton and carbon-13 NMR; assignments and correlations within the proton spin systems of the phenanthrenoid (CH) 4 and phenyl (CH)5 moieties are elucidated by the relatively quick COSY45 or COSY90 experiments; unexpected magnetic anisotropic shielding and deshielding effects are readily seen in proton spectra of adducts of N-alkyl maleimides. (Proton absorptions upfield of TMS can be observed.)
We wanted to take advantage of our NMR instrument’s ability to observe fluorine-19 (at 282 MHz) to provide stu-
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dents with spectra of another NMR-active nucleus. Starting from different fluorinated anilines, we have prepared the corresponding fluorinated maleamic acids, maleimides, and phencyclone adducts (with fluorines on the N-aryl ring). Our initial examination of the N-pentafluorophenyl adduct revealed five separate fluorine signals in the fluorine NMR, indicating hindered rotation of the pentafluorophenyl ring (10, 11). Homonuclear F–F COSY was used to assign the fluorine signals. Somewhat broadened fluorine signals for the corresponding maleamic acid (at ambient temperature) encouraged us to examine variable-temperature fluorine spectra, observing temperature-dependent behavior which we are exploring further; other fluorinated phenyl maleamic acids have shown remarkably broad fluorine resonances. Clearly, some interesting exchange phenomena are present. In the last year or so, we have introduced the use of molecular modeling software for use by our organic chemistry students and by our graduate students. Applications to numerous compounds in the series described above and to simplified model compounds have permitted students to perform semi-empirical and ab initio geometry optimizations and energy calculations, thus achieving a better understanding of nonbonded interactions and hindered molecular motions (19). Acknowledgment We are indebted to the National Science Foundation for partial support of these activities, especially for funding (in part) the purchase of our FT-NMR spectrometer. Additional support has been provided by the U.S. Education Department Minority Science Improvement Program.
Literature Cited 1. LaPlanche, L. A.; Xu, Y.; Benshafrut, R.; Rothchild, R.; Harrison, E. A., Jr. Spectrosc. Lett. 1993, 26, 79–101. 2. Xu, Y.; LaPlanche, L.; Rothchild, R. Spectrosc. Lett. 1993, 26, 179– 196. 3. Callahan, R.; Bynum, K.; Prip, R.; Rothchild, R. Chem. Educator 1998, 3, S1430–4171. The Chemical Educator Home Page. http://journals.springer-ny.com/chedr (accessed July 1999). 4. Benshafrut, R.; Callahan, R.; Rothchild, R. Spectrosc. Lett. 1993, 26, 1875–1888. 5. Callahan, R.; Rothchild, R.; Wyss, H. Spectrosc. Lett. 1993, 26, 1681–1693. 6. Bynum, K.; Rothchild, R. Spectrosc. Lett. 1996, 29, 1599–1619. 7. Bynum, K.; Rothchild, R. Spectrosc. Lett. 1996, 29, 1621–1634. 8. Bynum, K.; Rothchild, R. Spectrosc. Lett. 1997, 30, 727–749. 9. Bynum, K.; Rothchild, R. Spectrosc. Lett. 1997, 30, 1713–1732. 10. Amin, M. F.; Bynum, K.; Callahan, R.; Prip, R.; Rothchild, R. Spectrosc. Lett. 1998, 31, 673–692. 11. Bynum, K.; Prip, R.; Callahan, R.; Rothchild, R. J. Fluorine Chem. 1998, 90, 39–46. 12. Boccia, G. Callahan, R.; Prip, R.; Rothchild, R. Spectrosc. Lett. 1998, 31, 1367–1378. 13. Bynum, K.; Rothchild, R.; Shariff, N. Spectrosc. Lett. 1998, 31, 1379–1394. 14. Harrison, E. A., Jr. J. Chem. Educ. 1991, 68, 426–427. See footnote 5 therein. 15. Harrison, E. A., Jr. J. Chem. Educ. 1992, 69, 571. See footnote 5 therein. 16. Forsyth, W. R.; Weisenburger, G. A.; Field, K. W. Trans. Ill. State Acad. Sci. 1996, 89, 37-40. 17. Sasaki, T.; Kanematsu, K.; Iizuka, K. J. Org. Chem. 1976, 41, 1105–1112. 18. Wang, Z. Y. Synth. Commun. 1990, 20, 1607–1610. 19. For example, MacSpartan and PC Spartan; WaveFunction, Inc.: Irvine, CA, 1996–1997.
Ronald Callahan is in the Chemistry Department, New York University, 569 Brown Building, Washington Place, New York, NY 10003; phone: 212/998-8411; e-mail:
[email protected] or
[email protected]. Lawrence Kobilinsky is at John Jay College, 899 Tenth Avenue, New York, NY 10019; phone: 212/237-8884; email: LKJJJ@CUNYVM. CUNY.edu. Robert Rothchild is at John Jay College, 445 West 59th St., New York, NY 10019; phone: 212/237-8886; e-mail:
[email protected].
7 8
6
O
O H
5
O
+
N
R
O
N
CO 4
R
H 1
3
O
2
1 Phencyclone
Maleimide
2 Adduct
Scheme 1.
2
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