In the Laboratory
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Student-Determined Values for the Calculation of Chemical Shifts of Methylene Protons in Different Chemical Environments Gary W. Breton Department of Chemistry, Berry College, P.O. Box 495016, Mount Berry, GA 30149–5016;
[email protected] Nuclear magnetic resonance (NMR) spectroscopy has gained a place of preeminence in chemistry among methods of molecular structure determination (1–3). Its use is prevalent in both academic (i.e., graduate schools) and industrial settings. It is therefore vitally important that undergraduate chemistry majors be familiar with the basic experimental techniques and spectral interpretive skills associated with NMR spectroscopy. We introduce 1H NMR spectroscopy in the first semester of our organic chemistry course in conjunction with the relevant chapter from the textbook. An elementary (and brief ) discussion of the theory of instrument operation is followed by an in-depth discussion on the topics of chemical environment, chemical shift, and spin–spin coupling. The concept of chemical shift is reinforced by the introduction of a table (see Table 1) that allows for the rapid calculation of approximate chemical shifts for methyl, methylene, and methine protons in a variety of common chemical environments. Similar tables are readily available in the literature (4–6 ). Since this is an introduction to 1H NMR spectroscopy, we focus primarily on simple organic compounds with single functional groups and generally consider only the effect of α-substituents on chemical shift. (Even with this approximation, most calculations using the data in Table 1 are reliable to within 0.5 ppm.) We have found that the students are quite amazed at how easy it is to calculate the predicted chemical shift of any given proton environment using the table. We desired an experiment for the associated laboratory course (which we try to run conceptually “parallel” to lecture) that would demonstrate the effect of different commonly encountered chemical environments on chemical shift. We found, however, that with few exceptions (7–10), most widely used laboratory texts and many introductory experiments from this Journal (11–13) tend to introduce 1H NMR spectroscopy as a means of analysis for products derived from a reaction.1 The student’s initial use of 1H NMR spectroscopy, therefore, is relegated to secondary importance in an otherwise unrelated experiment that constitutes the primary focus of the lab exercise. We concluded that a new experiment was in order that had as its primary focus the operation of the NMR spectrometer and interpretation of representative spectra. Furthermore, we decided that it would be instructive for the students to construct a table for the calculation of chemical shifts—such as the one used in the lecture portion of the class (i.e., Table 1)—using spectral data obtained on their own. Selection of Compounds to Be Studied A series of propyl-substituted compounds from a variety of compound classes was selected for investigation. These compounds are listed in Table 2. Each compound may be conveniently represented in the form CH3CH 2CH 2–G,
Table 1. Table for Calculating Approximate Chemical Shifts for Methyl, Methylene, and Methine Protons Chemical Environment
Methyla (CH3–)
Methyleneb,c (RCH2–)
Methinec,d (R2CH–)
CHn– C=C
0.7
0.9
1.0
CHn–Ar
1.4
1.3
1.5
CHn–(CO)R
1.3
1.0
1.2
CHn–(CO)Ar
1.7
1.4
1.8
CHn–(CO)OR
1.1
0.9
1.0
CHn–(CO)OAr
1.5
0.9
—
CHn–(CO)NR2
1.1
0.8
0.8
CHn– OR
2.4
2.0
2.2
CHn– OH
2.4
2.2
2.4
CHn– O(CO)R
2.8
2.7
3.3
CHn– NR2
1.4
1.1
1.3
CHn– NO2
3.4
3.0
3.2
CHn– Cl
—
2.3
2.6
CHn–Br
—
2.1
2.8
CHn– I
—
1.8
2.8
CHn–C N
—
0.9
1.2
NOTE: Selected data from a table compiled by Dwight Kinzer at Berry College from spectral data found in ref 14. The tabulated data apply to acyclic compounds. All values in ppm relative to TMS at δ 0.0. aCalculated by adding the shift parameter to a base value of δ 0.9. bCalculated by adding the shift parameter to a base value of δ 1.4. cFor two neighbors, reduce the sum of the shift parameters by 20%. dCalculated by adding the shift increment to a base value of δ 1.5.
Table 2. Observed Chemical Shifts Compound Name
Functional Group, G (CH3CH2CH2–G)
n- Propylbenzene
– Ar [Ar = Ph]
δ a for –CH2–G 2.6
4- Heptanone
– (CO)R [R = n -pr]
2.3
Methyl butyrate
– (CO)OR [R = Me]
2.2
Dipropyl ether
– OR [R = n -pr]
3.3
1- Propanol
– OH
3.5
n- Propyl acetate
– O(CO)R [R = Me]
3.9
Tripropylamine
– NR2 [R = n -pr]
2.3
1- Nitropropane
– NO2
4.3
1- Chloropropane
– Cl
3.4
1- Bromopropane
– Br
3.3
1- Iodopropane
–I
3.1
Hexane
– R [R = n -pr]
1.3
aChemical shift (ppm) at 60 MHz in CCl , relative to TMS; an average 4 of 5–6 experimentally determined values obtained by students in Berry College’s Organic Chemistry course.
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In the Laboratory
where G is a functional group (Table 2, column 2). This representation accentuates the similarity among the compounds while at the same time highlighting the functional groups responsible for the different chemical environments. The propyl group of each compound gives rise to three distinct multiplets in the 1H NMR spectra. The terminal methyl group appears farthest upfield as a well-defined triplet, the central methylene as a hextet, and the —CH2–G protons as a downfield triplet. The compounds tripropyl amine, 4-heptanone, and dipropyl ether contain more than one propyl group apiece. However, as a result of the symmetry of these compounds the multiple propyl groups are chemically equivalent and only one set of signals is observed. This selection of compounds has the advantage that the student may focus solely on the effect of different chemical environments on the chemical shift of a common CH2 signal without the added complication of varying coupling patterns. Hexane was selected as a “reference” compound. It may be represented as two fused propyl groups, in analogy to the other compounds (i.e., “G” = n-propyl). Since all eight methylene protons of hexane appear as a single broad multiplet in the 1H NMR spectrum, the central maximum was taken as the “base” chemical shift for the “unshifted” methylene protons of a simple alkane (δ 1.3). Some minor complications are encountered in the spectra of propyl benzene (aromatic protons at δ 7.1), methyl butyrate (the methyl ester signal at δ 3.6), and propyl acetate (acetate signal at δ 2.0), but the simplicity of the patterns from these additional signals (all appear as singlets) makes them particularly easy to identify and account for. Experimental Procedure The class (typically 18–20 students per laboratory) was divided into groups of six. Each group was to obtain the 1H NMR spectra of all 12 compounds, and each student was responsible for running at least two samples, which were readily prepared by mixing in an NMR tube 0.10 mL of sample with 0.40 mL of a 2% solution of TMS in CCl4 (prepared in advance). Students then loaded their sample into the NMR magnet and collected and processed their own data. The NMR spectrometer we used was a Varian EM360 (60 MHz) that was upgraded to Fourier transform capability.2 Included with the upgrade as part of the package software was a subroutine that allows the student to obtain a spectrum (including integration and peak picking) in less than a minute using only three keystrokes. The rapid collection time minimized the time that students spent waiting in line to use the instrument. We found that students were generally comfortable with sample preparation and instrument operation after running the second sample. Results and Conclusion After obtaining all the spectra the groups were asked to identify the various chemical environments for each compound and assign them to the observed chemical shifts in the 1H NMR spectra. They were also responsible for ensuring that the integration signals were consistent with the compound’s structure. Chemical shifts for the methylene signals of interest (i.e., the triplet of the —CH2–G protons) were compiled into a table such as that shown in Table 2 (column 3). The 82
Table 3. Experimentally Determined and Literature ␣-Parameter Values for Methylene Protons α-Parameter/ppm a Functional Group This Work Beauchamp (4) Friedrich (5) – Ar
1.3
1.3
1.3
–(CO)R
1.0
1.1
1.0
–(CO)OR
0.9
1.0
1.0
– OR
2.0
2.0
1.9
– OH
2.2
2.2
2.1
– O(CO)R
2.6
2.7
2.5
– NR2
1.0
1.4
1.1
– NO2
3.0
3.1
2.9
–Cl
2.1
2.1
2.0
– Br
2.0
2.0
1.8
–I
1.8
1.9
1.7
aFor
this work chemical shift was calculated by adding the shift parameter to a base value for methylene protons of δ 1.3. Literature values were corrected to a base value for methylene protons at δ 1.3.
data in Table 2 represent the average of actual values obtained by students. The last entry in the table is the chemical shift for the methylene protons of the reference compound hexane. Subtraction of the “base” chemical shift of these protons from the corresponding shifts of each of the other compounds affords the α-substituent parameter for each chemical environment (Table 3, column 2). Immediately recognizable to the students upon completing these calculations is the wide range of parameter values induced by different chemical environments upon the αmethylene protons. There are many factors involved in the explanation of the effect that each of the groups “G” has on the chemical shift of the adjacent methylene protons, including various electronegativity and anisotropic effects. A detailed discussion of these factors is beyond the scope of this paper but may be found elsewhere (15). However, some generalizations concerning the relationship of chemical shift to chemical environment may be made upon examination of the data in Table 2. For example, the effect of electronegativity on chemical shift may be observed by comparing the chemical shifts of the methylene protons adjacent to the halogen in the compound series chloropropane, bromopropane, and iodopropane (Table 2). An increase in the magnitude of the chemical shift is observed with an increase in the electronegativity of the halogen (i.e., Cl > Br > I) (16). More generally, it is observed that protons on carbons directly attached to electronegative atoms or groups of atoms (e.g., halogens, –OR, –OH, –NO2) appear in the 3–4-ppm range. Aromatic rings and carbon– oxygen double bonds (of ketones, esters, etc.) have a lesser deshielding effect than directly attached heteroatoms, and methylene protons in these environments appear in the 2–3ppm range. These effects are discussed with the students as they interpret the various spectra and are reinforced by questions in the laboratory report. Of particular satisfaction to the students was the close agreement of their experimentally determined α -parameter values with those in Table 1 (column 2). As can be seen from Table 3, reasonably good agreement between the studentdetermined values and literature values was obtained (the
Journal of Chemical Education • Vol. 77 No. 1 January 2000 • JChemEd.chem.wisc.edu
In the Laboratory
literature values in Table 3 were corrected to the same chemical shift base value for the methylene protons used in this experiment [1.3 ppm]). Differences between values may be attributed to the fact that the literature data are generally taken as an average shift of a number of related compounds, whereas the student values are single determinations. Feedback from the students concerning this experiment has been positive. They are generally very pleased with the agreement of their data with the literature data. Their confidence in sample preparation and instrument operation increased with each sample run. They had ample time to interpret their spectra, and they were quite active in group discussions. This trend continued throughout the year, as they were expected to run 1H NMR spectra on a regular basis to characterize reaction products. As a result of the success of this project, we are currently devising similar instrument-focused introductory experiments for gas chromatography, infrared spectroscopy, and UV–vis spectroscopy.
Notes
Acknowledgments
10.
Partial support for this work was provided by the National Science Foundation’s Division of Undergraduate Education through DUE Grant # 9750684. Additional support was provided by the 1998 Camille and Henry Dreyfus Special Grant Program in the Chemical Sciences.
11.
W
Supplemental Material
Supplemental material for this article is available in this issue of JCE Online.
1. From a random survey of nine recent laboratory textbooks, only three had introductory NMR lab experiments (generally simple analysis of a known or an “unknown” compound ) other than employing NMR as a means of product analysis. 2. Purchased from Anasazi Instruments Inc.; Indianapolis, IN.
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