NMR-化学位移

NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities Hugo E. Gottlieb,* Vadim Kotlyar, and Abraham Nudelman* Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel Received June 27, 1997 In the course of the routine use of NMR as an aid for organic chemistry, a day-to-day problem is the identifica- tion of signals deriving from common contaminants (water, solvents, stabilizers, oils) in less-than-analyti- cally-pure samples. This data may be available in the literature, but the time involved in searching for it may be considerable. Another issue is the concentration dependence of chemical shifts (especially 1H); results obtained two or three decades ago usually refer to much more concentrated samples, and run at lower magnetic fields, than today’s practice. We therefore decided to collect 1H and 13C chemical shifts of what are, in our experience, the most popular “extra peaks” in a variety of commonly used NMR solvents, in the hope that this will be of assistance to the practicing chemist. Experimental Section NMR spectra were taken in a Bruker DPX-300 instrument (300.1 and 75.5 MHz for 1H and 13C, respectively). Unless otherwise indicated, all were run at room temperature (24 ( 1 °C). For the experiments in the last section of this paper, probe temperatures were measured with a calibrated Eurotherm 840/T digital thermometer, connected to a thermocouple which was introduced into an NMR tube filled with mineral oil to ap- proximately the same level as a typical sample. At each temperature, the D2O samples were left to equilibrate for at least 10 min before the data were collected. In order to avoid having to obtain hundreds of spectra, we prepared seven stock solutions containing approximately equal amounts of several of our entries, chosen in such a way as to prevent intermolecular interactions and possible ambiguities in assignment. Solution 1: acetone, tert-butyl methyl ether, di- methylformamide, ethanol, toluene. Solution 2: benzene, di- methyl sulfoxide, ethyl acetate, methanol. Solution 3: acetic acid, chloroform, diethyl ether, 2-propanol, tetrahydrofuran. Solution 4: acetonitrile, dichloromethane, dioxane, n-hexane, HMPA. Solution 5: 1,2-dichloroethane, ethyl methyl ketone, n-pentane, pyridine. Solution 6: tert-butyl alcohol, BHT, cyclo- hexane, 1,2-dimethoxyethane, nitromethane, silicone grease, triethylamine. Solution 7: diglyme, dimethylacetamide, ethyl- ene glycol, “grease” (engine oil). For D2O. Solution 1: acetone, tert-butyl methyl ether, dimethylformamide, ethanol, 2-propanol. Solution 2: dimethyl sulfoxide, ethyl acetate, ethylene glycol, methanol. Solution 3: acetonitrile, diglyme, dioxane, HMPA, pyridine. Solution 4: 1,2-dimethoxyethane, dimethylacetamide, ethyl methyl ketone, triethylamine. Solution 5: acetic acid, tert- butyl alcohol, diethyl ether, tetrahydrofuran. In D2O and CD3OD nitromethane was run separately, as the protons exchanged with deuterium in presence of triethylamine. Results Proton Spectra (Table 1). A sample of 0.6 mL of the solvent, containing 1 íL of TMS,1 was first run on its own. From this spectrum we determined the chemical shifts of the solvent residual peak2 and the water peak. It should be noted that the latter is quite temperature- dependent (vide infra). Also, any potential hydrogen- bond acceptor will tend to shift the water signal down- field; this is particularly true for nonpolar solvents. In contrast, in e.g. DMSO the water is already strongly hydrogen-bonded to the solvent, and solutes have only a negligible effect on its chemical shift. This is also true for D2O; the chemical shift of the residual HDO is very temperature-dependent (vide infra) but, maybe counter- intuitively, remarkably solute (and pH) independent. We then added 3 íL of one of our stock solutions to the NMR tube. The chemical shifts were read and are presented in Table 1. Except where indicated, the coupling constants, and therefore the peak shapes, are essentially solvent-independent and are presented only once. For D2O as a solvent, the accepted reference peak (ä ) 0) is the methyl signal of the sodium salt of 3-(trimeth- ylsilyl)propanesulfonic acid; one crystal of this was added to each NMR tube. This material has several disadvan- tages, however: it is not volatile, so it cannot be readily eliminated if the sample has to be recovered. In addition, unless one purchases it in the relatively expensive deuterated form, it adds three more signals to the spectrum (methylenes 1, 2, and 3 appear at 2.91, 1.76, and 0.63 ppm, respectively). We suggest that the re- sidual HDO peak be used as a secondary reference; we find that if the effects of temperature are taken into account (vide infra), this is very reproducible. For D2O, we used a different set of stock solutions, since many of the less polar substrates are not significantly water- soluble (see Table 1). We also ran sodium acetate and sodium formate (chemical shifts: 1.90 and 8.44 ppm, respectively). Carbon Spectra (Table 2). To each tube, 50 íL of the stock solution and 3 íL of TMS1 were added. The solvent chemical shifts3 were obtained from the spectra containing the solutes, and the ranges of chemical shifts (1) For recommendations on the publication of NMR data, see: IUPAC Commission on Molecular Structure and Spectroscopy. Pure Appl. Chem. 1972, 29, 627; 1976, 45, 217. (2) I.e., the signal of the proton for the isotopomer with one less deuterium than the perdeuterated material, e.g., CHCl3 in CDCl3 or C6D5H in C6D6. Except for CHCl3, the splitting due to JHD is typically observed (to a good approximation, it is 1/6.5 of the value of the corresponding JHH). For CHD2 groups (deuterated acetone, DMSO, acetonitrile), this signal is a 1:2:3:2:1 quintet with a splitting of ca. 2 Hz. (3) In contrast to what was said in note 2, in the 13C spectra the solvent signal is due to the perdeuterated isotopomer, and the one- bond couplings to deuterium are always observable (ca. 20-30 Hz). Figure 1. Chemical shift of HDO as a function of tempera- ture. 7512 J. Org. Chem. 1997, 62, 7512-7515 S0022-3263(97)01176-6 CCC: $14.00 © 1997 American Chemical Society show their degree of variability. Occasionally, in order to distinguish between peaks whose assignment was ambiguous, a further 1-2 íL of a specific substrate were added and the spectra run again. Table 1. 1H NMR Data proton mult CDCl3 (CD3)2CO (CD3)2SO C6D6 CD3CN CD3OD D2O solvent residual peak 7.26 2.05 2.50 7.16 1.94 3.31 4.79 H2O s 1.56 2.84a 3.33a 0.40 2.13 4.87 acetic acid CH3 s 2.10 1.96 1.91 1.55 1.96 1.99 2.08 acetone CH3 s 2.17 2.09 2.09 1.55 2.08 2.15 2.22 acetonitrile CH3 s 2.10 2.05 2.07 1.55 1.96 2.03 2.06 benzene CH s 7.36 7.36 7.37 7.15 7.37 7.33 tert-butyl alcohol CH3 s 1.28 1.18 1.11 1.05 1.16 1.40 1.24 OHc s 4.19 1.55 2.18 tert-butyl methyl ether CCH3 s 1.19 1.13 1.11 1.07 1.14 1.15 1.21 OCH3 s 3.22 3.13 3.08 3.04 3.13 3.20 3.22 BHTb ArH s 6.98 6.96 6.87 7.05 6.97 6.92 OHc s 5.01 6.65 4.79 5.20 ArCH3 s 2.27 2.22 2.18 2.24 2.22 2.21 ArC(CH3)3 s 1.43 1.41 1.36 1.38 1.39 1.40 chloroform CH s 7.26 8.02 8.32 6.15 7.58 7.90 cyclohexane CH2 s 1.43 1.43 1.40 1.40 1.44 1.45 1,2-dichloroethane CH2 s 3.73 3.87 3.90 2.90 3.81 3.78 dichloromethane CH2 s 5.30 5.63 5.76 4.27 5.44 5.49 diethyl ether CH3 t, 7 1.21 1.11 1.09 1.11 1.12 1.18 1.17 CH2 q, 7 3.48 3.41 3.38 3.26 3.42 3.49 3.56 diglyme CH2 m 3.65 3.56 3.51 3.46 3.53 3.61 3.67 CH2 m 3.57 3.47 3.38 3.34 3.45 3.58 3.61 OCH3 s 3.39 3.28 3.24 3.11 3.29 3.35 3.37 1,2-dimethoxyethane CH3 s 3.40 3.28 3.24 3.12 3.28 3.35 3.37 CH2 s 3.55 3.46 3.43 3.33 3.45 3.52 3.60 dimethylacetamide CH3CO s 2.09 1.97 1.96 1.60 1.97 2.07 2.08 NCH3 s 3.02 3.00 2.94 2.57 2.96 3.31 3.06 NCH3 s 2.94 2.83 2.78 2.05 2.83 2.92 2.90 dimethylformamide CH s 8.02 7.96 7.95 7.63 7.92 7.97 7.92 CH3 s 2.96 2.94 2.89 2.36 2.89 2.99 3.01 CH3 s 2.88 2.78 2.73 1.86 2.77 2.86 2.85 dimethyl sulfoxide CH3 s 2.62 2.52 2.54 1.68 2.50 2.65 2.71 dioxane CH2 s 3.71 3.59 3.57 3.35 3.60 3.66 3.75 ethanol CH3 t, 7 1.25 1.12 1.06 0.96 1.12 1.19 1.17 CH2 q, 7d 3.72 3.57 3.44 3.34 3.54 3.60 3.65 OH sc,d 1.32 3.39 4.63 2.47 ethyl acetate CH3CO s 2.05 1.97 1.99 1.65 1.97 2.01 2.07 CH2CH3 q, 7 4.12 4.05 4.03 3.89 4.06 4.09 4.14 CH2CH3 t, 7 1.26 1.20 1.17 0.92 1.20 1.24 1.24 ethyl methyl ketone CH3CO s 2.14 2.07 2.07 1.58 2.06 2.12 2.19 CH2CH3 q, 7 2.46 2.45 2.43 1.81 2.43 2.50 3.18 CH2CH3 t, 7 1.06 0.96 0.91 0.85 0.96 1.01 1.26 ethylene glycol CH se 3.76 3.28 3.34 3.41 3.51 3.59 3.65 “grease” f CH3 m 0.86 0.87 0.92 0.86 0.88 CH2 br s 1.26 1.29 1.36 1.27 1.29 n-hexane CH3 t 0.88 0.88 0.86 0.89 0.89 0.90 CH2 m 1.26 1.28 1.25 1.24 1.28 1.29 HMPAg CH3 d, 9.5 2.65 2.59 2.53 2.40 2.57 2.64 2.61 methanol CH3 sh 3.49 3.31 3.16 3.07 3.28 3.34 3.34 OH sc,h 1.09 3.12 4.01 2.16 nitromethane CH3 s 4.33 4.43 4.42 2.94 4.31 4.34 4.40 n-pentane CH3 t, 7 0.88 0.88 0.86 0.87 0.89 0.90 CH2 m 1.27 1.27 1.27 1.23 1.29 1.29 2-propanol CH3 d, 6 1.22 1.10 1.04 0.95 1.09 1.50 1.17 CH sep, 6 4.04 3.90 3.78 3.67 3.87 3.92 4.02 pyridine CH(2) m 8.62 8.58 8.58 8.53 8.57 8.53 8.52 CH(3) m 7.29 7.35 7.39 6.66 7.33 7.44 7.45 CH(4) m 7.68 7.76 7.79 6.98 7.73 7.85 7.87 silicone greasei CH3 s 0.07 0.13 0.29 0.08 0.10 tetrahydrofuran CH2 m 1.85 1.79 1.76 1.40 1.80 1.87 1.88 CH2O m 3.76 3.63 3.60 3.57 3.64 3.71 3.74 toluene CH3 s 2.36 2.32 2.30 2.11 2.33 2.32 CH(o/p) m 7.17 7.1-7.2 7.18 7.02 7.1-7.3 7.16 CH(m) m 7.25 7.1-7.2 7.25 7.13 7.1-7.3 7.16 triethylamine CH3 t,7 1.03 0.96 0.93 0.96 0.96 1.05 0.99 CH2 q, 7 2.53 2.45 2.43 2.40 2.45 2.58 2.57 a In these solvents the intermolecular rate of exchange is slow enough that a peak due to HDO is usually also observed; it appears at 2.81 and 3.30 ppm in acetone and DMSO, respectively. In the former solvent, it is often seen as a 1:1:1 triplet, with 2JH,D ) 1 Hz. b 2,6-Dimethyl-4-tert-butylphenol. c The signals from exchangeable protons were not always identified. d In some cases (see note a), the coupling interaction between the CH2 and the OH protons may be observed (J ) 5 Hz). e In CD3CN, the OH proton was seen as a multiplet at ä 2.69, and extra coupling was also apparent on the methylene peak. f Long-chain, linear aliphatic hydrocarbons. Their solubility in DMSO was too low to give visible peaks. g Hexamethylphosphoramide. h In some cases (see notes a, d), the coupling interaction between the CH3 and the OH protons may be observed (J ) 5.5 Hz). i Poly(dimethylsiloxane). Its solubility in DMSO was too low to give visible peaks. Notes J. Org. Chem., Vol. 62, No. 21, 1997 7513 lizhongyu 高亮 lizhongyu 高亮 Table 2. 13C NMR Dataa CDCl3 (CD3)2CO (CD3)2SO C6D6 CD3CN CD3OD D2O solvent signals 77.16 ( 0.06 29.84 ( 0.01 39.52 ( 0.06 128.06 ( 0.02 1.32 ( 0.02 49.00(0.01 206.26 ( 0.13 118.26 ( 0.02 acetic acid CO 175.99 172.31 171.93 175.82 173.21 175.11 177.21 CH3 20.81 20.51 20.95 20.37 20.73 20.56 21.03 acetone CO 207.07 205.87 206.31 204.43 207.43 209.67 215.94 CH3 30.92 30.60 30.56 30.14 30.91 30.67 30.89 acetonitrile CN 116.43 117.60 117.91 116.02 118.26 118.06 119.68 CH3 1.89 1.12 1.03 0.20 1.79 0.85 1.47 benzene CH 128.37 129.15 128.30 128.62 129.32 129.34 tert-butyl alcohol C 69.15 68.13 66.88 68.19 68.74 69.40 70.36 CH3 31.25 30.72 30.38 30.47 30.68 30.91 30.29 tert-butyl methyl ether OCH3 49.45 49.35 48.70 49.19 49.52 49.66 49.37 C 72.87 72.81 72.04 72.40 73.17 74.32 75.62 CCH3 26.99 27.24 26.79 27.09 27.28 27.22 26.60 BHT C(1) 151.55 152.51 151.47 152.05 152.42 152.85 C(2) 135.87 138.19 139.12 136.08 138.13 139.09 CH(3) 125.55 129.05 127.97 128.52 129.61 129.49 C(4) 128.27 126.03 124.85 125.83 126.38 126.11 CH3Ar 21.20 21.31 20.97 21.40 21.23 21.38 CH3C 30.33 31.61 31.25 31.34 31.50 31.15 C 34.25 35.00 34.33 34.35 35.05 35.36 chloroform CH 77.36 79.19 79.16 77.79 79.17 79.44 cyclohexane CH2 26.94 27.51 26.33 27.23 27.63 27.96 1,2-dichloroethane CH2 43.50 45.25 45.02 43.59 45.54 45.11 dichloromethane CH2 53.52 54.95 54.84 53.46 55.32 54.78 diethyl ether CH3 15.20 15.78 15.12 15.46 15.63 15.46 14.77 CH2 65.91 66.12 62.05 65.94 66.32 66.88 66.42 diglyme CH3 59.01 58.77 57.98 58.66 58.90 59.06 58.67 CH2 70.51 71.03 69.54 70.87 70.99 71.33 70.05 CH2 71.90 72.63 71.25 72.35 72.63 72.92 71.63 1,2-dimethoxyethane CH3 59.08 58.45 58.01 58.68 58.89 59.06 58.67 CH2 71.84 72.47 17.07 72.21 72.47 72.72 71.49 dimethylacetamide CH3 21.53 21.51 21.29 21.16 21.76 21.32 21.09 CO 171.07 170.61 169.54 169.95 171.31 173.32 174.57 NCH3 35.28 34.89 37.38 34.67 35.17 35.50 35.03 NCH3 38.13 37.92 34.42 37.03 38.26 38.43 38.76 dimethylformamide CH 162.62 162.79 162.29 162.13 163.31 164.73 165.53 CH3 36.50 36.15 35.73 35.25 36.57 36.89 37.54 CH3 31.45 31.03 30.73 30.72 31.32 31.61 32.03 dimethyl sulfoxide CH3 40.76 41.23 40.45 40.03 41.31 40.45 39.39 dioxane CH2 67.14 67.60 66.36 67.16 67.72 68.11 67.19 ethanol CH3 18.41 18.89 18.51 18.72 18.80 18.40 17.47 CH2 58.28 57.72 56.07 57.86 57.96 58.26 58.05 ethyl acetate CH3CO 21.04 20.83 20.68 20.56 21.16 20.88 21.15 CO 171.36 170.96 170.31 170.44 171.68 172.89 175.26 CH2 60.49 60.56 59.74 60.21 60.98 61.50 62.32 CH3 14.19 14.50 14.40 14.19 14.54 14.49 13.92 ethyl methyl ketone CH3CO 29.49 29.30 29.26 28.56 29.60 29.39 29.49 CO 209.56 208.30 208.72 206.55 209.88 212.16 218.43 CH2CH3 36.89 36.75 35.83 36.36 37.09 37.34 37.27 CH2CH3 7.86 8.03 7.61 7.91 8.14 8.09 7.87 ethylene glycol CH2 63.79 64.26 62.76 64.34 64.22 64.30 63.17 “grease” CH2 29.76 30.73 29.20 30.21 30.86 31.29 n-hexane CH3 14.14 14.34 13.88 14.32 14.43 14.45 CH2(2) 22.70 23.28 22.05 23.04 23.40 23.68 CH2(3) 31.64 32.30 30.95 31.96 32.36 32.73 HMPAb CH3 36.87 37.04 36.42 36.88 37.10 37.00 36.46 methanol CH3 50.41 49.77 48.59 49.97 49.90 49.86 49.50c nitromethane CH3 62.50 63.21 63.28 61.16 63.66 63.08 63.22 n-pentane CH3 14.08 14.29 13.28 14.25 14.37 14.39 CH2(2) 22.38 22.98 21.70 22.72 23.08 23.38 CH2(3) 34.16 34.83 33.48 34.45 34.89 35.30 2-propanol CH3 25.14 25.67 25.43 25.18 25.55 25.27 24.38 CH 64.50 63.85 64.92 64.23 64.30 64.71 64.88 pyridine CH(2) 149.90 150.67 149.58 150.27 150.76 150.07 149.18 CH(3) 123.75 124.57 123.84 123.58 127.76 125.53 125.12 CH(4) 135.96 136.56 136.05 135.28 136.89 138.35 138.27 silicone grease CH3 1.04 1.40 1.38 2.10 tetrahydrofuran CH2 25.62 26.15 25.14 25.72 26.27 26.48 25.67 CH2O 67.97 68.07 67.03 67.80 68.33 68.83 68.68 toluene CH3 21.46 21.46 20.99 21.10 21.50 21.50 C(i) 137.89 138.48 137.35 137.91 138.90 138.85 CH(o) 129.07 129.76 128.88 129.33 129.94 129.91 CH(m) 128.26 129.03 128.18 128.56 129.23 129.20 CH(p) 125.33 126.12 125.29 125.68 126.28 126.29 triethylamine CH3 11.61 12.49 11.74 12.35 12.38 11.09 9.07 CH2 46.25 47.07 45.74 46.77 47.10 46.96 47.19 a See footnotes for Table 1. b 2JPC ) 3 Hz. c Reference material; see text. 7514 J. Org. Chem., Vol. 62, No. 21, 1997 Notes For D2O solutions there is no accepted reference for carbon chemical shifts. We suggest the addition of a drop of methanol, and the position of its signal to be defined as 49.50 ppm; on this basis, the entries in Table 2 were recorded. The chemical shifts thus obtained are, on the whole, very similar to those for the other solvents. Alternatively, we suggest the use of dioxane when the methanol peak is expected to fall in a crowded area of the spectrum. We also report the chemical shifts of sodium formate (171.67 ppm), sodium acetate (182.02 and 23.97 ppm), sodium carbonate (168.88 ppm), sodium bicarbonate (161.08 ppm), and sodium 3-(trimethylsilyl)- propanesulfonate [54.90, 19.66, 15.56 (methylenes 1, 2, and 3, respectively), and -2.04 ppm (methyls)], in D2O. Temperature Dependence of HDO Chemical Shifts. We recorded the 1H spectrum of a sample of D2O, containing a crystal of sodium 3-(trimethylsilyl)propane- sulfonate as reference, as a function of temperature. The data are shown in Figure 1. The solid line connecting the experimental points corresponds to the equation which reproduces the measured values to better than 1 ppb. For the 0 - 50oC range, the simpler gives values correct to 10 ppb. For both equations, T is the temperature in °C. Acknowledgment. Generous support for this work by the Minerva Foundation and the Otto Mayerhoff Center for the Study of Drug-Receptor Interactions at Bar-Ilan University is gratefully acknowledged. JO971176V ä ) 5.060 - 0.0122T + (2.11 � 10-5)T2 (1) ä ) 5.051 - 0.0111T (2) Notes J. Org. Chem., Vol. 62, No. 21, 1997 7515