Solving Molecular Structures Using NMR and Molecular Mechanics An Undergraduate Research Project Erin L. Anderson, Du Li, and Noel L. Owen Brigham Young University, Provo, UT 84602 Nuclear magnetic resonance spectroscopy (NMR)has become one of most valuable ex~erimentaltechniaues available to the organic chemist fa> unraveling the stkcture of complex compounds.' The phenomenal development of NMR over the past ten or 15 years a s a structural tool for the chemist is due mainly to the advent of Fourier transform techniques and to the introduction of new pulse sequences that have introduced an amazing degree of specificity in the analysis of the resonance signals. Application to Undergraduate Curriculum Indeed, such is the importance of NMR as a spectroscopic tool that quite extensive laboratory sessions, a s well a s lectures on the basic theory, are included in most universitv undereraduate chemistrv courses. As with manv other sophistiLated experimentai techniques, NMR can b i used for solvine .,numerous structural Droblems bv relative nov~ces-that 19, undergraduates-when the b a s ~ cground rules are followed 'I'h~sh a w ~ntroductloncan be found in most physical and organic chemistry texts. Over the same 15 vears. molecular mechanics calcnlations have also foundincre&ing applicability in structural orzanic chemistrv. These ~ a c k a e e sallow the ~ o t e n t i aenl ergy of a compou~dto be minimized by systematic adjustments in the molecular geometry. Several standard software packages (e.g., MM2)' are currently available. They provide a new method whereby equilibrium molecular structures can he deduced. We will describe here a n experimental project that combines the use of NMR and these software packages in a
complementary way. I t can he used to train undergraduate students in molecular structure. The Structural Problem We have used several different compounds in this research project a s examples of species whose structural features are not clear-cut (e.g., sugars and sterically hindered phosphites). When studying these compounds, interesting questions arise that are associated with their overall geometry. For illustration, we will describe one of the phosphites, tris(2,4-di-t-butylpheny1)phosphite(DBPP) (Fig. I), which is a crystalline solid used commercially a s an "antioxidant" in polymers.3 The three phenyl rings that are bonded to the PO3 group are substituted with very bulky t-butyl groups a t the ortho and para positions. The structure as a whole represents a sterically "cmwded" molecule. The research problem in this instance was to establish the geometry of this compound using NMR spectroscopy and molecular-modelling calculations. Since the molecule contains three identical groups attached to the central phosphorus atom, the student might expect that molecular symmetry could, in principle, simplify the spectra considerably. This could be true--unless, of course, that symmetry is destroyed by steric or other factors! The Experimental Equipment All 'H and 13C NMR spectra were obtained using a 200MHz superconducting spectrometer (Varian Gemini). Samples were run as dilute solutions in CDC13 with about 50 mg in 0.7 mL of solvent. A trace of tetramethylsilane (TMS) was used as a n internal reference standard. The 31P spectra were run on a 500-MHz instrument (Varian VXR)because our Gemini spectrometer is set up for 'H and 13C signals only. The Gemini 200 is made available to all students for "hands-on" use once they have taken a basic course on using the instrument. However, the spectra run on the 500-MHz instrument are always obtained by a trained operator. All model calculations were carried out by undergraduate students on a PC that had 640 kB of RAM and 20-MB 'All current textbook- of oraanic chemistrv include sections - ~ ~, ~ - on - ~the use of NMR spectroscopy for structure determination. For a description of FT-NMR, see, for example, King, R. W.; Williams. K. R. J. Chem. Ed. 1989,66,A213; 1989, 66, A243; 1990,67,A93;1990,67, A214. '(a) Burkert, U.; Aliinger, N. L. Molecular Mechanics, ACS monoaraoh 177. Washinaton. DC. 1982. lbl Manv new software oackaaes hv&in(l fiolecula;meihanics and 'ikoroo;atina NMR data are cur,~~ renl y being deveopeo.See, for example. Olalson, B D.: Mar~sn. J.: A M L Sc.enlslrcCompufingandAulomanon 1991. Feb, p 47 %Jr samples of lr s 2.4-d#-l-b~1j pneny pnospmte and lrs(2.4-d-1amylpheny1)phosphitewere provided by Byron Hunter (Uniroyal) ~~
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Figure 1. Structure of tris(2,4-di-1-butylphenyl)phosphite.
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ABMX ( HaHbHmP ) Ha = 7.29 ppm Hb = 7.09 ppm Hm= 7.36 ppm p =
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J(ab) = 8.5 Hz J(bm)= 2.4 Hz J(aP) = 1.9 Hz
Figure 2. (a) 'H NMR spectrum of tris(2,4-di-t-butylphenyl)phosphite;(b) expansion of the 7.S7.5ppm region of spectrum a; (c) simulated 'H spectrum for an ABMX system between 7.0and 7.5ppm; (d)3 ' spectrum ~ of tris(2,4-di-t-butylpheny1)phosphite. of hard disk capacity I t incorporated a math coprocessor and used the program PCMODEL." Results and Learning Experiences The Aliphatic Region A preliminary appraisal of the 'H spectrum of DBPP (Fig. 2) quickly showed both expected and unexpected signals. Only two strong lines are seen in the aliphaticregion, and they a r e obviously due to the equivalent methyl groups of the two t-butyl groups. This implies that the two different methyl groups on each of the three phenyl rings are in identical magnetic environments for each ring. The question "Why do the methyl groups of a t-butyl group give identical signals?" introduces the phenomenon of internal rotation and average NMR signals. I t offers a good teaching opportunity for those students who are curious. The Aromatic Region On the other hand, in the aromatic region there are five peaks--each of which appears a s a d o u b l e t d u e to the three hydrogens attached to each ring. I t is difficult to ra4PCMODEL (version 3.0),Serena Software, Box 3076,Bloomington, IN 47402. 5The interaction between the meta hydrogen atoms of the aromatic rings in this compound (J(@, = 2.4 Hz) represents a very nice example of "W 4-bond coupling in molecules.
tionalize how three hydrogens could give rise to such a complex pattern-if the rings are equivalent. We would expect the two adjacent hydrogens, which are ortho and meta to the oxygen atom, to couple strongly. We would also expect the two hydrogens in the meta positions to show coupling.5 However, any interaction between hydrogen atoms that are five bonds apart would be too small to be observed in the spectrum. From the appearan& of the splitting and the intensity oattern ofthese five doublets. the first set ofstudent rxplahations include the following suggestions.
The sample is not pure. The molecular structure is not symmetrical Same "second-order"coupling interactions are present. Accurate caupling constants can be obtained by expanding the "aromatic" region (Fig. 2b). The 13cSpectrum At this stage the student is encouraged to study the "C spectrum (Fig. 3), which shows 11 peaks. The two large peaks a t about 3 1 ppm obviously represent the aliphatic methyl carbons of the two t-butyl groups. The other two close signals a t about 35 ppm, which are about one third as intense a s the former, correspond to the quaternary carbons of the t-butyl groups. This also indicates that only two different sets of methyl groups are present. However, the aromatic region contains seven peaks, and each ring only has six carbons! Also, some of the peaks apVolume 69 Number 10 October 1992
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Figure 3.% NMR spectrum (and spectral expansion) of tris(2,4-di-1-butylphenyl)phosphite.
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near to be broader in shane than mieht be exnected. This brings up the former question: Are the rings identical or does the strong steric hindrance affect the svmmetrv of the whole structure.
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Molecular Modelling Usine the molecular-modeline nromam. the students can now investigate the p o s s i b i l ~ ~at n&ymmetrical h~ structure has a lower overall enerw than the svmmetrical structure, in which all three pheng groups are orientated the same way. The result of this exercise shows that the energy of a n initial nonsymmetrical configuration, which is typically over 1400 kcavmol, can be significantly reduced to approximately 57 kcallmol. It also shows that this minimum corresponds to a symmetric structure in which the three aromatic rings are identically orientated to the central phosphite group. Solving the Riddle It is instructive to challenge the students to minimize this energy, using different structural starting parameters. Thus, they gain an appreciation for the role played by 6(a)Mark. V.; D~ngan, C. H.: Cruicnfled. M. M.: Van Wazer, ,. R. In Toprcs In Phosphorous Chemwtry: Grayson. M.; Gnnm E. J., Eas; ntencence: New York. 1983 Vol 5 pp 227-429; (b) Cr~lcnftelo. M. M.; Dungan, C. H.; Van Wazer, J. R. In Topics in Phosphorous Chemist~ Gravson, M.: Griffith, E. J.. Eds: Interscience: New York. 1983:
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pitfalls in the whole modelling procedure. Armed with the results of the molecular mechanics calculation, the students now have constraints, and they must consider all other possible reasons why the NMR spectra (both 'Hand have unusual features. This includes the possible presence of impurities in the samnle. A check of the meltine noint (185 0.5 "C). .. which occ'rs cleanly over a very short temperature interval, helps to convince the student that it is unlikely that a major impurity component caused the spectral anomalies. Eventually the student will realize that nuclei other than 'H and 13Ccan also show NMR spectra when placed in magnetic fields. These other nuclei might also interact with the 'H and 13Cnuclei. This appears to be a nontrivial step for many students because NMR lectures in chemistry concentrate almost entirely on the two most frequently used nuclei. Also, most students already know that the other nuclei that are commonly found in organic comare inactive in the NMR context. pounds (12Cand 0"') However 31Phas a spin of one half and a natural abundance of 100%. I t couples strongly6 to both 'H and 13C. There are several different ways for students to c o n f i i that the complexity seen in the hydrogen and carbon spectra is caused by coupling to the phosphorus atom. If an NMR spectrometer capable of detecting 31Presonances is available, the proton-coupled phosphorus spectrum may be viewed directly (Fig. 2c). Then the measured coupling can be compared directly with that observed in the hydrogen spectrum. Alternatively, a 'H spectral simulation experiment may be carried out for a ABMX system. (This facility is com-
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manly available on most FT-NMR spectrometers.) Figure 2d illustrates that a perfect match with the experimental spectrum can be generated, thus confirming the cause of the unusual NMR features. For the students, this emphasizes the importance of considering all magnetic nuclei in a compound. This match between observed and calculated spectrum is attained only if the 31P-1H(a) coupling constant (J(,, = 1.9 Hz) is incorporated into the simulation data. Additional insights
One aspect of the NMR spectra in this project puzzles some students: When studying the 'H spectrum, the effect of the phosphorus nucleus on the hydrogen spectrnm can be observed. whereas the corres~onding13C interactions are absent. Also, the 13C spectrum shows the effect of the phosphorus, whereas the reverse is not true. This is a good opportunity to explain about the differences in thcbcrccntige population ofthe various nuclei in natural abundance. Students also learn that most "C spectra are normally displayed with all 'H interactions dr'Assignmen1 of the I3C lnes was carred OJI sing DEPT. dETCOR, ano long-ran e dETCOR exper ments I1 1s nteresrlng lo note that the slrongesr 'P-" C COJP mg (18.31rlzj is lo Cta,. dowever. wln Clo) an0 C(d)are spll oy 3.6 ano 1 8 dz, respeclve y.
coupled. The assignments for both the 'Hand the I3C spectral lines are given in Figures 2 and 3, re~pectively.~ Conclusions We have found that this project provides a good opportunity for undergraduates to become familiar with modem NMR methods and molecular-modeling techniques. They can also become reasonably proficient the techniques introduced. They begin to appreciate how the application of different experimental methods, when used in concert, can help to explain and unravel complex questions of structure or geometry in molecular systems. Students see that such problems would be much more difficult to solve using just one method. In addition, specfic compounds can be used to introduce students to features or concents in NMR soectrosco~vthat they would not likely encounter in normal undergraduate lectures. An e x a m ~ l eis t-butvl Dhos~hites.as illustrated by tris(2,4-di-t-b~
