In the Laboratory
The Discovery Approach to NMR: Development of ChemicalShift Additivity Tables and Application to Product Identification Eric Bosch Department of Chemistry, Southwest Missouri State University, Springfield, MO 65804-0087;
[email protected] NMR spectroscopy is the premier tool for structure elucidation in organic chemistry and as such is presented in both one- and two-semester organic courses. The three major concepts used in NMR structure determination, namely, chemical-shift correlation tables, proton–proton coupling (splitting of peaks), and the integration of peaks, are routinely presented in organic chemistry texts (1), and as the use of NMR spectroscopy has become more widespread 1H NMR spectra are often recorded in organic labs as an integral part of product identification (2). This presentation is designed to give students insight into the development of NMR spectral prediction software that uses empirical chemical-shift additivity tables to predict the NMR spectra of complex molecules.1 We describe the development of a simple chemical-shift additivity table and its use to predict the 1H NMR spectrum of methyl 3-nitrobenzoate. This presentation may be adopted as a prelab exercise coupled to a common undergraduate experiment, the nitration of methyl benzoate (3). Variations in the magnitude of proton–proton coupling around a benzene ring is first used to assign each hydrogen resonance in the 1H NMR spectrum of 1,3-dinitrobenzene. These assignments are then used to develop a chemical-shift additivity table for nitro-substituted benzenes. Finally, this table is used to predict the 1H NMR spectrum of methyl 3-nitrobenzoate. Background The unsaturated nature of the benzene nucleus allows for long-range magnetization transfer and thus coupling is observed between ortho, meta, and para hydrogens. The magnitude of the proton–proton coupling diminishes in proportion to the distance between the coupled protons. Consequently ortho coupling is strong ( J ∼8 Hz), meta coupling moderate ( J ∼2 Hz), and para coupling weak ( J < 1 Hz), as in Figure 1 (4 ). On 200- or 300-MHz NMR instruments the weak para coupling is generally not observed, and in this presentation we will ignore para coupling, considering only the ortho and meta coupling. Spectral Assignment of 1,3-Dinitrobenzene The variation in magnitude of the coupling constant in substituted benzenes as described above is used to predict the
multiplicity (appearance) of each peak in the proton NMR spectrum of a well-known, well-characterized compound, 1,3-dinitrobenzene (5). Direct comparison of the predicted peak multiplicity to the actual spectrum then allows the assignment of each peak in the proton NMR spectrum of 1,3-dinitrobenzene to protons, Ha, Hb, and Hc, respectively, as shown in the structure below: NO2 Hb
Ha
Hc
NO2 Hb
Proton Ha, between the two nitro groups, has no ortho H’s and is thus only coupled (long range) to the two meta hydrogens (Hb). The signal for Ha will therefore appear as a narrow triplet with J ∼2 Hz. The chemically equivalent protons Hb are each ortho to one nitro group and para to the other nitro group. These protons are coupled to the common ortho hydrogen Hc as well as the meta hydrogen Ha. Since the ortho coupling is about 8 Hz and the meta coupling (long-range) is about 2 Hz, the peak is expected to appear as a doublet ( J ∼2 Hz) of a doublet ( J ∼8 Hz). Finally, proton Hc is meta to both nitro groups and is only coupled to the two chemically equivalent ortho H’s, Hb, and is therefore expected to be a wide triplet with J ∼8 Hz. The predicted appearance of the three peaks is shown in Figure 2. Thus although both Ha and Hc both appear as triplets, the magnitude of the coupling constant easily allows us to assign each peak in the 1H NMR spectrum: Hc is a wide triplet, while Ha is a narrow triplet. The actual 1H NMR spectrum of 1,3-dinitrobenzene is shown in Figure 3 (6 ). Thus, on the basis only of the appearance (splitting) of the peaks, we can assign the chemical shifts of the protons Ha, Hb, and Hc as 9.06, 8.60, and 7.85 ppm, respectively. Chemical Shift Additivity Table In order to prepare a chemical shift additivity table we will assume that the chemical shift of each of the three hydrogens Ha, Hb, and Hc is a function of only two factors:
Jortho = 6-9 Hz Ha
H
Hb (2 protons) ~8 Hz
H
H
Hc
~2 Hz
~2 Hz
Jpara < 1 Hz
~8 Hz
H
H H
Jmeta = 1-2.5 Hz
Figure 1. Typical proton–proton coupling around a benzene ring.
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Figure 2. Predicted splitting of the proton NMR signals for protons Ha , Hb , and Hc , respectively.
Journal of Chemical Education • Vol. 77 No. 7 July 2000 • JChemEd.chem.wisc.edu
In the Laboratory
(i) the benzene ring current, and (ii) the effect of substituents. Since the ring current is approximately the same for each of the protons, the actual chemical shift of each proton deviates from that of a hydrogen on unsubstituted benzene only as a result of the nitro substituent, which may be ortho, meta, or para to that hydrogen. The base chemical shift of 7.26 ppm is typical of benzene in chloroform. The effect of an ortho, meta, and para nitro group on the chemical shift of each of the protons Ha, Hb, and Hc can then be calculated. An easy place to start is the proton Ha. This proton is flanked by two ortho nitro groups and exhibits a chemical shift of 9.06 ppm. Assuming that the effect of each nitro group is the same, the effect of each ortho nitro group can be estimated as (9.06 – 7.26)/2 ppm or 0.90 ppm. Proton Hc has two meta nitro groups and the effect of each meta nitro group on the chemical shift of this proton is thus (7.85 – 7.26)/2 ppm or 0.30 ppm. Proton Hb is more complex because it is flanked by one ortho nitro group and has one para nitro group. Using the estimated contribution of the ortho nitro group on the chemical shift calculated above, the effect of the para nitro group is estimated as (8.60 – 7.26 – 0.90) ppm or 0.44 ppm. A similar set of values can be obtained by analysis of the proton NMR spectrum of dimethyl isophthalate (6 ). These values are collected in Table 1.2,3 Spectral Prediction In the final stage of this presentation the chemical shift additivities collected in Table 1 are used in conjunction with the relative magnitudes of the coupling constants given in Figure 1 to predict the proton NMR spectrum of the methyl 3-nitrobenzoate (see structure below, showing the labeling of the protons). NO2 Hd
Ha
Hc
CO2Me Hb
Chemical shift predictions are calculated starting from the base value for a proton on benzene and sequentially adding the effect of each of the substituents on the benzene ring as
Figure 3. Proton NMR spectrum of meta dinitrobenzene run on a Varian Gemini 200 MHz spectrophotometer.
Table 1. Chemical-Shift Additivites Derived for Nitro and Methylester Substitutuents Substituent
Position a ortho
meta
para
NO2
0.90 (0.95)
0.30 (0.17)
0.44 (0.33)
CO2 Me
0.71 (0.74)
0.14 (0.07)
0.25 (0.20)
aComparative
values in parentheses taken from ref 4 p 80.
presented in the table. Proton Ha has an ortho nitro group and an ortho methyl ester, and the chemical shift is predicted to be: Ha: δ = 7.26 (base value) + 0.90 (ortho NO2 group) + 0.71 (ortho CO2Me group) ppm = 8.96 ppm.
The chemical shifts of the other protons are calculated in the same way: Hb: δ = 7.26 (base value) + 0.44 (para NO2 group) + 0.71 (ortho CO2Me group) ppm = 8.41 ppm; Hc: δ = 7.26 (base value) + 0.30 (meta NO2 group) + 0.14 (meta CO2Me group) ppm = 7.70 ppm; and Hd: δ = 7.26 (base value) + 0.90 (ortho NO2 group) + 0.25 (para CO2Me group) ppm = 8.41 ppm.
The appearance of the individual peaks can be predicted using the magnitudes of the coupling constants given in Figure 1. Thus proton Ha is only coupled to the two meta hydrogens, Hb and Hd, and the peak is expected to appear as a narrow triplet with J ∼2 Hz. Proton Hc is coupled to the two ortho hydrogens, Hb and Hd, and thus is expected to appear as a wide triplet with J ∼8 Hz. Protons Hb and Hd are predicted to have similar chemical shifts, 8.41 ppm, and thus the peaks may overlap and be rather complex. The two wellseparated triplets, one wide at 7.72 ppm and one narrow at 8.96 ppm, then serve as diagnostic of the meta isomer. Comparison of this predicted spectrum with the recrystallized product from the nitration of methyl benzoate (3) shown in Figure 4 confirms the meta substitution pattern of the product. Indeed, the chemical shifts of protons Ha, Hb, Hc, and Hd are found to be 8.78, 8.32, 7.63, and 8.36 ppm, respectively.
Figure 4. Proton NMR spectrum of the crystalline product from the nitration of methyl benzoate showing the aromatic region. Not shown is the methyl ester peak (3H singlet) at 3.89 ppm.
JChemEd.chem.wisc.edu • Vol. 77 No. 7 July 2000 • Journal of Chemical Education
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In the Laboratory
Note 1. NMR predictive software is available from at least two vendors: Advanced Chemical Development (ACDLabs), 133 Richmond St. W., Suite 605, Toronto, ON M5H 2L3, Canada; and CambridgeSoft Corporation (ChemNMR), 100 Cambridge Park Drive, Cambridge, MA 02140. 2. 1H NMR data for dimethyl isophthalate are as follows: δ (CDCl3) 3.95 (s, 3H), 7.54 (t, J = 7.7 Hz, 1H), 8.23 (dd, J = 1.7 and 7.7 Hz, 1H), 8.67 (t, J = 1.7 Hz, 1H). 3. It should be noted that the chemical shift additivities taken from ref 4 were obtained by averaging chemical shifts from a large number of nitroarenes. Nevertheless, the deviation from those determined in this simple demonstration using only data from 1,3dinitrobenzene is relatively small, < 0.13 ppm.
Literature Cited 1. See for example: Solomons, T. W.; Fryle, C. B. Organic Chemistry, 7th ed.; Wiley: New York, 1999; pp 370–393. Brown, W. H.; Foote, C. S. Organic Chemistry, 2nd ed.; Saunders College: New York, 1998; pp 461–479. E g¯ e, S. Organic Chemistry, 4th ed.; Houghton Mifflin: New York, 1999; pp 461–479. Vollhardt, K. P. C.; Schore, N. E. Organic Chemistry, 3rd ed.; Freeman, New York, 1998; pp 384–417. Bruice, P. Y. Organic Chemistry, 2nd ed.; Prentice Hall: Englewood Cliffs, NJ, 1998; pp 522–557.
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2. See for example: Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Organic Laboratory Techniques, 3rd ed.; Saunders College: New York, 1999. Williamson, K. L. Macroscale and Microscale Organic Experiments, 3rd ed.; Houghton Mifflin: New York, 1999. Mohrig, J. R.; Morrill, T. C.; Hammond, C. N.; Neckers, D. C. Experimental Organic Chemistry; Freeman: New York, 1998. 3. See for example: Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Organic Laboratory Techniques, 3rd ed.; Saunders College: New York, 1999; pp 342–345. Williamson, K. L. Macroscale and Microscale Organic Experiments, 3rd ed.; Houghton Mifflin: New York, 1999; pp 355–359. 4. Macomber, R. S. A Complete Guide to Modern NMR Spectroscopy; Wiley-Interscience: New York, 1998. This is also described in the texts in refs 1 and 2. 5. The X-ray crystal structure of 1,3-dinitrobenzene was first published in 1947. Gregory, N. W.; Lassettre, E. N. J. Am. Chem. Soc. 1947, 69, 102–106. 6. There are several Internet sites from which spectral data can be downloaded and thus actual spectra do not need to be run. The National Institute of Materials and Chemical Research in Tsukuba, Japan has a large database of spectral data that can be accessed free of charge at: http://www.aist.go.jp/RIODB/ SDBS/sdbs/owa/sdbs_sea.cre_frame_sea (accessed May 2000). This database is widely used, having had 140,000 hits recorded in the month of September 1999 (personal communication from Kikuko Hayamizu, NIMC, Japan).
Journal of Chemical Education • Vol. 77 No. 7 July 2000 • JChemEd.chem.wisc.edu
