. George Glaros and Norman H. CromweU U n ~ v e r s ~of t y Nebraska
L~ncoln,68505
An Integrated NMR and Synthetic Organic chemistry Experiment
W i t h the current trend of int,roducing the use of nuclear magnetic resonance spectral techniques into the undergraduate chemistry course it seems to be of value to seek ways of integrating the study of nmr spectra with the normal synthetic laboratory program. We suggest here a synthetic sequence which involves procedures of general utility, but which give products having nmr spectra illustrative of basic principles. The sequence given might be best suited for an organic preparations course since one step requires a rather long reaction time and would require the use of a vapor hood, as hydrogen sulfide is liberated in one step. The sequence requires three vacuum distillations and would cause some inconvenience if performed by a large class, but the remaining steps are straightforward and easily performed. The sequence is given below. The experimental procedures used have previously been described in the literature (1-5).
Figure 1 .
NMR spectrum of 4-methyl-4-phenyl-Z-pent~n~ne.
The second step employs the Willgerodt reaction which is a general reaction not often employed in undergraduate courses (t, 3 ) . The initially formed thiomorpholide is not very soluble in the common nmr solvents, but the acid, 4-methyl-4-phenyl-pentanoic acid, which is formed upon hydrolysis is soluble in carbon tetrachloridc and gives a somewhat surprising spectrum, shown in Figure 2. It can be seen that the
CHa
I I
Ph-C-CH,CH,CO,H
PPA +
CH,
The first react,ion is a Friedel-Craft alkylation (1) and the product, 4-methyl-4-phenyl-2-pentanone has a very simple spectrum as illustrated in Figure 1. The carbonyl group deshields the terminal methyl group enough so that it appears a t approximately 35 Hz downfield from the geminal dimethyls and consequently the spectrum consists of three singlets upfield and the phenyl protons far downfield, centered at 435 Hz. 854 1 Journal of Chemical Education
Figure 2. NMR spectrum of 4-methyl-4-phenylpenttnoic acid.
two methylene groups have the same chemical shift and therefore one obtains a singlet a t 117 Hz. Too often one might overlook the possibility that two protons, though chemically nonequivalent, can be magnetically equivalent. Another example of this is the spectrum of methyl acetylene, which shows one singlet (6). The importance of integration of the peaks is emphasized by the fact that all four methylene protons give rise to this singlet. Chemical exchange can also be illustrated by adding a drop of deuterium oxide and observing the loss of the acid proton which is far downfield at about 730 Hz (7). The next step can be performed by several ways. In this laboratory polyphosphoric acid is used to obtain the 4,4dimethyl-1-tetralone from ring closure of the acid ( 3 ) . This reaction can be performed in a beaker in a very short time. If a different pathway is desired,
L Figure 3.
NMR spectrum of 4.4-dimethyl-1-tetralone.
the acid can be transformed to the acid chloride by thionyl chloride and the tetralone obtained by reaction of the acid chloride wit.h aluminum chloride (8). The tetralone has been well studied (4) and Figure 3 illustrates several important aspects of the nmr spectrum. One very important observation is that the aromatic ring proton p to the carbongl is strongly deshielded, not just by an inductive or resonance effect, but by the diamagnetic anisotropy of the carbonyl group (8). Since the carbonyl group is held in position, in the plane of the benzene rmg, this proton is deshielded enough to shift it from the area of the rest of the benzene ring protons. The next obvious fact is that this proton is not a simple singlet or even a doublet as Figure 4 illustrates. It appears as a multiplet which can roughly be analyzed using a metric ruler or calipers to illustrate coupling between ortho, meta, .and para protons in a benzene ring. The coupling constants in a benzene ring are as follows: J(ortho) = G-10 Hz, J(meta) = 2-3 Hz, and J(para) = 1 Hz (9). The rationalization given in
Figure 4 can be done by the student and does not require a computer calculation to obtain satisfactory results. The nmr spectrum of the tetralone also contains an example of an AzBzpattern between 100-175 Hz. The spectrum of the two methylene groups is not just a pair of triplets but one can see evidence of higher order splitting, as illustrated in Figure 5. The signal for the two methyl groups illustrates a general principle by virtue of their giving rise to a singlet. The cyclohexenone ring system exists primarily in two chair conformations which can interconvert rapidly enough a t room temperature to average out the field experienced by each so they appear as a singlet (4, 10).
The next reaction is a widely used condensation, the Claisen-Schmidt reaction (4). This one is particularly good because the product is slightly soluble in ethanol, and it readily crystallizes from the reaction mixture and can he filtered off and washed free of the two starting materials, which are liquids. The reaction occurs very rapidly and can be worked up after one half an hour with good yields. The nmr spectrum of 2-benzal4,4-dimethyl-1-tetralone, Figure 6, illustrates allylic coupling (4). The methylene protons appear at 175 Ha, as a closely spaced doublet due to the coupling with the olefin J = 2-3 Hz.
Figure 6.
Figure 4. Expandon of orornotic ring proton rnethvl-1 -tetralone.
0
to corbonyl in 4,4-di-
NMR spectrum 2-benrol-4,4-dimethyI-1.tetralone.
In the final step of this sequence the b e n d tetralone is brominated with N-bromosuccinimidc (6). The initially formed radical rearranges before abstracting a bromine atom as illustrated below (6).
q,. q, CHPh
CHPh I
Figure 5.
Expansion of methylene pmtonr in 4.4.dimethyl-1-tetrolone.
The nmr spectrum (4), Figure 7, shows two separate singlets for the methyl groups, since they are now magVolume 46, Number 12, December 1969
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855
change the structure of a molecule and observe the sometimes surprising changes in the nmr spectrum. It is hoped that this paper will stimulate others to integrate the different aspects of organic chemistry taught in the lecture room with those taught in the laboratory. Acknowledgmenl
Figure 7. NMR rpectwm of 2-la-bmmobenryll-4,4-dimethyl-l,4-dihydm-1-ketonaphthaiene. Insert is on expansion of the melhine proton obror-
This work was supported in part by a special Departmental Science Development Award to the Department of Chemistry from the National Science Foundation, Grant No. GU-2054.
bance.
Liferotwe Cited
netically nonequivalent due to the lack of mobility in the ring system and the presence of the 2-(a-bromobenayl) group. The methine proton is isolated at 384 Ha and is split by the olefin proton giving rise to a very closely spaced doublet. The splitting can be observed a t a sweep width of 50 Ha. It should be stressed that this sequence of reactions may not be ideal for all organic chemistry laboratories. The Willgerodt reaction requires a vapor hood and a long reaction time. Also the three vacuum distillations may put a strain on available equipment, hut the integration of theory and practical examples is important. All of the principles illustrated in this discussion could be established with other compounds, but this sequence of reactions allows the student to
(1) HOFFMAN, A,, J . Am. ~ h m~ .o c .51, , 2542 (igzg). R. D., AND CROMWELL, N. H., J . Am. C h m . (2) CAMPBELL, Soc., 77, 5169 (1955). N. H.. J. 0 7 ~ Chm.. . (3) . . Brim. V. L.. AND CROMWELL. . 23,789 . (1959). (4) IMBACH, J. L., POHLAND, A. E., WEILER,E. D., AND CROMWELL,N. H., T~tmhedmn,33, 3931 (1967). N. H., AND WU, E., J . 0rg. Chem., 33, 1895 (5) CROMWELL, (1968). (6) NMR Spectra Catalog, Compiled by BAHACCA, N. S., D. D., JOHNSON, L. F.,PIER,E. A., AND SHOO& HOLLIS, ERY,J. N., Varim Assaci~tes,1962, 1963, spectra B16. L. M., "Applications of Nuclear Magnetic Reso(7) JACKMAN, nance Spectroscopy in Organic Chemistry," Pergamon Press, London, 1959, p. 71. (8) Reference (7), p. 124. (9) Reference (7), p. 85. (10) Reference (7), p. 11.5.
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