Structure, Chirality, and FT-NMR in Sophomore Organic Chemistry A Modern Approach to Teaching Orville L. Chapman and Arlene A. Russell University of California, Los Angeles, CA 90024 Two major evils plague organic chemistry teaching strategy. First, we teach organic structure and the orbital basis for structure concurrently. Second, we combine chirality and stereochemistry. In each case, we bombard the students with two major concepts simultaneously. Modernizing Our Approach Why should we approach organic structure from a theoretical perspective? We deduce structure from experimental information, especially nuclear magnetic resonance spectra. Why do we separate chirality from fundamental structure, where it belongs? We do so because we do not introduce symmetry properties in presenting structure. Change in organic chemistry teaching strategy must begin with an assessment of what is important today. Nuclear magnetic resonance spectroscopy is the most important structural tool in chemistry. NMR provides the daily bread of synthetic chemists. For physical organic chemists, it defines exchange phenomena and conformational equilibria. NMR probes many aspects of chemistry The first structural information chemists obtain for any soluble compound comes from NMR, and this is now increasingly true for solids as well. Molecular complexation, DNA-small molecule binding, and protein structure--all profit from modem NMR techniques. NMR imaging was discovered by Paul Lauterbur-a chemist, not a physician. It represents one of chemistry's great contributions to society in this century ( I ) . Medical imaging, biochemical imaging, and industrial imaging illustrate the significance of Lauterbur's discovery (2).Everything that happens in NMR today depends on Fourier transform spectroscopy. Why do we teach undergraduates continuous-wave (CW) 60-MHz proton spectroscopy? We teach CW proton spectroscopy for many reasons. Fourier transform instruments are expensive, and both instrument time and data processing time are limited. Also, we faculty members grew up with CW proton spectroscopy and are comfortable with it. If NMR spectroscopy comprises one of the most important structural tools in chemistry, why does this subject receive such short shrift in organic chemistry courses? Modem NMR spectroscopy poses a challenge not only to the student but to the faculty as well. The time has come. Instruction must change! In an age of space exploration, organ transplants, and genetic engineering, 19th century 'We introduce symmetry using examples from art, architecture, flowers,hub caps, baskets, pottery, rugs, and fabrics. Chemistry thus begins with a new topic that builds on students' prior nonchemical experience. Students have access to an interactive Hypercard program, A Guided Tow of Symmetry, by Owille L. Chapman. This program is available from Alpha-Omega, Inc. 2~~~~ stands for distortionless enhanced polarization transfer. 'Contact the authors for further information about the slides that support this lecture strategy.
chemistry can not compete. If we do not take our students to the forefront of every facet of chemistry and if we do not speak of the chemistry that will be-instead of what has been-chemistry, as a science, will cease to progress. The Experimental Ap roach to Teaching Organic gtructure Organic chemistry courses must begin with structure. But why begin with orbitals and hybridization? Consider an experimental approach-use NMR. Introduce your students to symmetry axes and planes;' these concepts are fundamental to all aspects of structure, not just to stereochemistry. Remind your students of the valence of hydrogen and the first-row elements, and give them the equation for calculating the number of sites of unsaturation from the molecular formula. Your students learned about molecular formulasin first-vear chemistm Exolain that roto on-decou~led carbon spec& show one peak f i r each type of carbon; [ymmetry-related carbons give a single peak. Next, tell them about '3C(1HtDEFT spectra2that are obtained using 135' and 90' read-pulse angles (3,4).You can describe the experimental details later. Give them the results now. Show them how DEPT spectra3 reveal the number of hydrogens attached to each type of carbon using the logic table shown in Figure 1.Do not worry about chemical shifts for now. Proton Dewupled Carban
DEPT 135
DEPTSO
Figure 1. Logic table for ''C{'H]DEPT spectra. Classroom Work Use symmetry. Have your students bring their molecular model kits to class, and give the students problems. A Compound with the Formula CGHIZ
A compound with the formula C6H12 and one site of unsaturation shows a single peak in the proton-decoupled carbon spectrum (Fig. 2). The DEFT 1 3 r spectrum shows a single negative peak, and the 90' DEPT spectrum shows no signal at all. All six carbons are identical, and each has two hydrogens. Given the valence of carbon and hydrogen, each carbon must bond to two other identical carbons. Simple logic dictates a ring of six methylene groups: cyclohexane. Students quickly realize that six CH2 groups Volume 69 Number 10 October 1992
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Pmtondecouplec Carton I
DEPT 135
I
I
n
high
low
I
i g Field
Field
I
DEPT 90
h
low
high Field
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Figure 2. %MR and '
3
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spectra ~ ) ~ of C6HI2. ~ ~ ~
can only form a ring, and they can construct a model. Let vourstudents takc a few minutes to help eachother get the model together. Talking reinforces what they are learning. A Compound with the Formula C5Hiz
Now give your students a second problem: a compound with the formula C5HI2and no sites of unsaturation. The proton-decoupled carbon s p e c t m shows two peaks4 (Fig. 3). At 1 3 5 ~ the DEPT spectrum shows one positive peak, but a t 9V no peaks appear.
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Proton-decouplec Carbon b
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~~
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DEPT 90
7
low
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high
low
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Students encounter structural isomerism here for the first time. Two wmpounds with the formula CsH12 have very different spectra-and consequently different structures. Another Compound with the Formula C5Hl2
Reconsider the formula C5H1z in a compoound that has no unsaturation. Now four carbon signals are observed: one CH, one CH2,and two CH3 signals (Fig. 5). The molecule has twelve hydrogens. Thus, one of the CH3 signals must represent two methyl groups; the molecule must have some element of symmetry. The pieces are clear: (CH& CH3 CH2 CH Only one assembly is possible: (CH&CHCHzCH3, which has a plane of symmetry. Proton-dewupled O
low
I
DEPT 135
DEPT 90
,
high
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low
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Figure 3. '%MR and ' 3 ~ ( ' spectra ~ ) of ~ C5H12. ~ ~ ~
Figure 5. ' ~ M and R '3~('H)DEPT spectra of C5H12
Of the two types of carbon that are present, one type has no hydrogens, and the other type has three hydrogens. Since the molecule has five carbons and twelve hydrogens, four of the carbons must be CH3 groups. Thus, the structure must be C(CH& Students solve this problem quickly. How many ways can you put four CH3groups on one carbon atom? Let them work together. Your students will generate considerable noise, but you have broken the passive-learning mold. The molecular models take care of the spatial aspects of structure. You can explain why later.
Your students have just encountered another example of structural isomerism. A Compound with the FormulaC4Hs
Now give the students a compound with the formula CaHs and two sites of unsaturation. The pieces are immediately clear (Fig. 6): C and CH, and the molecular formula requires two of each. Only one structure is possible: 2-butyne.
A Compound with the Formula C6H12
For the next problem, use a compound with the formula CsHlz and one site of unsaturation. The spectra (Fig. 4) resemble those in the previous problem except that the carbon with no hydrogens appears at low field rather than a t high field.
I
Proton-decoupled Carbon
I DEPT 135
a highl low 2 high
low
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Field
Proton-demupled
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b
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Figure 6. %MR and l3~{'H]DEPT spectra of C4He
DEPT 90
A Compound with the Formula C3H6
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~ ) ~of CsH12. ~ ~ ~ Figure 4. 13cMR and ' 3 ~ { ' spectra
Again, we must have four CH3 groups, but we now have two carbons that have no hydrogens. These carbons must bond to each other twice to satisify the carbon valence. Only one possibility exists:
Your students are now ready for a compound with the formula C3Hs and one site of unsaturation. The spectra (Fig. 7) reveal three identical methylene groups, and only cyclopropane fits this requirement. Explore the symmetry properties of cyclopropane with the students. Make sure thev see the 3-fold axis. the three vertical planes, and the horiLontal plane
I
Proton-decoupled Carbon
DEPT 135
DEPT SO
In the carbon spectra, o ~rhr s o Herence bothers st~de'ntsmucn les; ly members wno grew JP w tn proton speclra The than t qoes f a c ~ a fferenks in nlenslty arse from the vary ng n~mberof camons, the
1I
number of hydrogens on the different carbons,the decoupling power, and the pulse deiay.
Figure 7. ' ~ M and R '3~{'H)DEPT spectra of C3He
Students the - --- occasionallv ~, ask ~ about ~ ~ differences in oeak intensitv ~~
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II
Field
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14 high
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low
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I high
low
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A Compound with the Formula CsHs Now give your students a compound with the formula C6H6and four sites of unsaturation. This set of data (Fig. 8) leads to the conclusion that the compound has six identical CH groups. Only the two structures given in Figure 9 meet this requirement.
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Proton-dewupled Carbon
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Figure 11. '%MR and 1 3 ~ { 1 ~ J ~ ~ ~ o~ f C5H8. spectra
low high L low high
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When your students have completed building their models of 1,s-dimethylallene, have them look down the linear three-carbon system (Fig. 121, and put the methyl group nearest them up. Now ask how many of them have the remote methyl group to their right. Then ask how many have the remote methyl gmup to their left. The students divide approximately equally. Now have them work in pairs to make both models. Ask them to decide whether the molecules are identical. Do both structures fit the spectra? What symmetry properties
Figure 9. Isomers of C6H6that have only one type of CH group. Benzene is the correct answer because unsaturated carbons appear a t lower field than saturated carbons. Your students have already established this fact by experience.
Figure 12. Enantiomers of 1,3-dimethyiallene
Preparing Them for Higher Challenges You can now introduce chemical shifts. Give the students more practice structures as homework. The isomeric xylenes and ethylbenzene provide good examples. Your students know about alkanes, cycloalkanes, alkenes, alkynes, and aromatics. They understand structural isomerism, and they have approached fundamental concepts in a spirit of discovery. You can now tackle a special structure problem. A Special Structure Problem Start with a wmpound with the formula C3& and two sites of unsaturation. The proton-decoupled carbon spectrum (Fig. 10)shows two signals. The DEPT 13F spectrum shows only one negative peak, and the DEPT 90' spectrum shows no peaks a t all. We have one carbon with no hydrogens and two CH? groups. The wmpound is allene. Now give them a wmpound with the formula C& and
I
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DEFT 135
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DEFT 90
b
low
high
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Figure 10. %MR and '
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two sites of unsaturation (Fig. 11). This compound has one carbon without hydrogens, two CH groups, and two methyl groups. Clearly it has some element of symmetry. Either 2,2-dimethylcyclopropene or 1,3-dimethylallene fit formally, but the low-field carbon that has no hydrogens can only belong to 1,3-dimethylallene.
do the two molecules have? How do the two structures relate to each other? Expect chaos. These questions challenge students, and they respond. Most students realize quickly that the structures are not identical and that both fit the spectra. Finding the Cz axis proves more difficult, and relatively few students rewgnize the mirror-image relation. You are now in a position to defme chirality and to illustrate mirror images. At the end of this lecture, leave your students with the following question. Is it always true t h a t a mal?cule is c h i d if it has only one C, i d s and no other symmetry element?
The allene system makes an excellent first encounter with the concept of chirality because it uses only the knowledge of right and left. Summary At this stage, you have invested three lectures, and you are now in a position to give a molecular orbital explanation of structure that has real meaning. The students understand hydrocarbon structure on a broad basis; they know where structure comes from. Your students have become active participants in the lecture, and the laboratory now has real relevance. The Laboratory Experience Lab lectures develop basic NMR concepts including the Fourier transform experiment, chemical shifts, solvents, and reference compounds.5 Spin-spin splitting is introduced using proton-arbon and fluorine-earbon systems that are truly first-order. UCLA s t u d e n t s learn data processing using the PCNMRt p ~ o g r a mand , ~ they have access to a n IBM Instruments 200-MHz spectrometer. The student places a Volume 69 Number 10 October 1992
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sample in the sample chancer - and selects the desired spectra &om a menu. We also use FT-NMR PROBLEMS,? which is an interactive laser-video-disc propam, in the sophomore organic course. FT-NMR PROBLEMS provides a data base of more than six thousand real spectra obtained on FT spectrometers. These spectra are presented in problem format and comprise 48 compounds. The problems are grouped into 16 beginning problems, 16 intermediate problems, and 16 expert problems. The problems include alkanes, alkenes, alkynes, aromatics, alcohols, ketones, carboxylic acids, amides, esters, amines, halides, alkaloids, terpenes, heterocyclics, steroids, and synthetic intermediates. The NMR techniques include proton-decoupled carbon; gated decoupled carbon; DEPT at 45', go', and 135'; COSY; HETCOR; HETCOR long range; NOESY; INADEQUATE; 500-MHz proton; 200-MHz proton; 60-MHz proton; homonuclear proton decoupling; N-15; P-31; and F-19. Special Resources
The tutorial covers each technique a t the beginning level. Help is available for each technique within the problems. Chemical shift tables for carbon, proton, nitrogen, phosphorus, and fluorine are always available. A table of coupling constants can be called a t anytime. The student has many resources available. Furthermore, the student can call up special features including brain scans, NMH spectra of = living insect pupa, and a chart of the elements that shows the nuclei that give NMR spectra. These unprecedented resources for the undergraduate are delivered without barriers. The program requires no instruction before use; it is completely transparent. No computer skills are required. The touch-screen monitor is the only input device. Thus, the student concentrates only on the problem. LaboratoryOrganization
The students work in p u p s of three. Articulation of scientific ideas, discussion of what each spectrum means, and defense of ideas contribute to learning. This also reduces the fear that comes when students encounter true problems for which they have neither paradigm nor algorithm. =At UCLA, we give the NMR lab lectures early in the sewnd quarter. We have no laboratory in the first quarter of organic chemistry. 6PCNMR+was wrinen at IBM Instruments and modified by T. Farrar at the Univerisity of Wisconsin. The program is availablethrough WiscWare at the University of Wisconsin and runs on IBM PC's. 'FT-NMRPROBLEMS was created by Arlene A. Russell and Orville L. Chapman in 1988. The program is available from AlphaOmega, Inc.. 3930 Mandeville Canyon Road, Los Angeles, CA 90049.
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This program presents a n exceptional means of developing higher-order thinking skills. Results at Different Levels Can sophomores handle organic chemistry at this level? Two tests show unambimously that sophomores can work effectively at this level. First, we gave a sophomore organic class one lecture on NMR using the approach just described. The class then had NMR structure ~roblemson every test. Sophomores were soon telling seniors how to solve their orgahic qualitative analysis unknowns. Carbon spectra, including DEPT spectra, have much more power than proton spectra in solving structure problems. Sewnd, we worked at the junior high school level. After instruction in symmetry, valence, proton-decoupled carbon spectra, and DEPT spectra, junior high students solved structure problems using real data. Conclusions What have we achieved? The introduction of structure is liberated from molecular orbital theory; symmetry now serves all of structure not iust stereochemistry. Chirality. freed from the complications of stereochemistry, has a place in teachine structure. Modem NMR methods are introduced early, a>d organic chemistry has an experimental basis. Students gain a deeper appreciation of chemical structure: deduction embeds structure in their minds. Chemical structure is no longer arbitrary; it derives naturally from experimental data. The relation between structure and s~ectrosconv has bewme axiomatic. *~ students comprehend modern NMR techniques. In addition, they gain a sense of participation in research and forefront instrumentation early in the chemistry curriculum. This experience develops a sense of entering the DTOfession. Students know that learning NMR makes research DOSsible; when they read journals, they see spectra that they recoenize. Finallv the eifted student. the for~ottenDenon in modern curriiula, Knds a real chdlenge;the stidents can actually achieve expert status. ~
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Acknowledament The national science foundation supported this work (CHE-8851478 and L'SE 91-50811. IBM Instruments donated the 200-MHz NMR spectrometer. Literature Cited 1. Lauterbur, P C.Nohrrs 1878,242. 190. 2. Moonen, C. T. W.: Van ZUI, P C. M.:Frank, J. A; Le Bihsn,D.; be eke^ E. D.S&nee, 1990, "Z" '.2r,
Dvdded.;. H.: Dietrich. W. Struefurs Eluddatian
bv Mo&m NMR, a Workbwk: ~ t e i n h p f f v d 0a a~k t a d t . S p r v l p ~ Y e r l ~NgN: ~ Y Y Y ~1989. , 4. Demme. A. E. Modam NMR m h n i w e s for ChPmishV Re-rch: Remmon Ross: 3.
New York, 1987.
