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Vicinal deuterium isotope effects on proton chemical shifts
IOURNAL
OF
MAGNETIC
RESONANCE
2, 47-49
(1970)
Vi&al Deuterium Isotope Effects on Proton Chemical Shifts* W. SAUR, H. L. CRESPI, AND J. J. KATZ Chemistry
Division,
Argonne
National
Laboratory,
Argonne,
Illinois
60439
ReceivedJuly 31, 1969; acceptedSeptember5, 1969 Vicinal isotope shifts are presented for a number of compounds, including ethyl and isopropyl acetates, lactic acid, and acetaldehyde. Upfield proton chemical shifts of from 0 to 15 x 1O-3ppm per vicinal deuteron are observed. Inverse substitution of 2H for ‘H leads to a remarkably different isotope shift per vicinal deuteron. INTRODUCTION In the course of experiments on the biosynthesis of partially deuterated ethanols (I), lactic acids (2), and other partially deuterated (isotope hybrid) metabolites, we have
observed a number of deuterium isotope effects on the chemical shift of neighboring protons. Of particular interest is the magnitude of some of the vicinal effects, as there appear to be few data on such deuterium isotope effects. A recent review (3) of isotope effects on chemical shifts indicates a need for more experimental observations if deuterium isotope effects on chemical shifts are to be understood. Table 1 lists our results for a number of partially deuterated compounds. These results may be summarized as follows: (1) geminate and vicinal substitution of ‘H by ‘H causes a ‘H upfield chemical shift that is linear with increasing deuterium substitution at equivalent positions; (2) for carbon atoms with tetrahedral geometry, the geminate isotope effect is 15-17 x 10e3 ppm upfield shift per deuteron in a variety of aliphatic and aromatic compounds; (3) for vicinal substitution, the isotope effect on methyl protons results in an upfield shift of 7.2 x 10T3 ppm per deuteron for deuterium substitution at the adjacent methylene or methine group. This value is observed in ethyl acetate, isopropyl acetate, lactic acid, and at the methyl group at position 1 in phycocyanobilin. An upfield shift of 6 x 10V3 ppm is observed in acetaldehyde. However, when the deuterium is substituted into the methyl group of these compounds, a much smaller vicinal effect (0 to 5 ppm per deuteron) on the hydrogen in the methylene or methine position is found. A similar result has been found by Allred and Wilk (4), i.e., (CH3)3CD (isotope shift 9 x 10m3 ppm) and (CD3),CH (isotope shift 1.3 x low3 ppm per deuterium). Marsman, Lubach and Drenth (5) find in acetoin vicinal isotope effects of 8 + 1 x 10m3 ppm in CH,CD(OH)COCH3 and 5 + 1 x low3 ppm in CH2DCH(OH)COCH,. In the ethylidene group at position 2 of phycocyanobilin, the unusually large vicinal effect may be related to the fact that the CHzD group is at the terminum of a highly con* Work performed under the auspicesof the U.S. Atomic Energy Commission. 47
48
SAUR,
DEIJTERIUM
ISOTOPE
CRESPI,
AND
KATZ
TABLE
1
EFFECTS
ON CHEMICAL
SHIFTS
Isotope effect, ppm X 103” Solvent
Conc’n Geminate
CH&HDOCOCH8 CH&D20COCH3 CD$ZH20COCH, CH,CDOHCOOH CHzDCDOHCOOH CHD,CDOHCOOH CHDzCHOHCOOH CDzCHOHCOOH (CD&CHOCH3 (CH&CDOCH, Ar-CH,D Ar-CHD2 CH2=CDOCOCH, CHD=CHOCOCH3 CHzDCHO CH,CDO In phycocyanobilin: Pos. 1: CHa-CD Pos. 2: CHZD-CH=
CCI,
10%
NDCI
0.4 M
Vicinal
16
7 8 5.3 7.4 * 0.3 7.0 * 0.3 7.1 + 0.3 4.3 * 0.3 4.2 & 0.3 4.5 6.5
16.2 f 0.3 16.2 & 0.3
10%
ccl,
Noteb
0.1 M
16.7 i 0.6 16.1 f 0.6
Neat c
cis,
12 Neat c
17
0; tram,
5.0
cis, 0; tram,
13
0
6 Pyridinede
0.1 M
7.2 f 0.5 15 f 2
a All isotope effects listed as per deuterium atom. b These measurements are the average of the four ring methyl groups of phycocyanobilin (in pyridine-d,) and the 1 and 3 methyl groups of methylpheophorbide a (in CDC13). For the structure of the tetrapyrrole compounds, see (7) and (8). c With 50% tetramethylsilane.
jugated system. While our results are consistent with the idea that a deuterium atom is a better electron donor than lH (6), a satisfactory explanation of the nonequivalence of the vicinal isotope effects described here is lacking. As pointed out by Batiz-Hernandez and Bernheim (3) the theoretical explanation of the deuterium isotope effect on proton chemical shifts is in an unsatisfactory state. The isotope shift appears to be the result of small changes in bond length or angle and in contributions from intramolecular electric fields, as well as possible changes in the distribution of molecules over vibrational energy states. Additional data on vicinal isotope shifts should help to delineate the important parameters in the shifts and so to make possible the use of this isotope effect as a tool for the study of molecular structure. EXPERIMENTAL
The partially deuterated lactates were obtained by biosynthesis (2). The partially deuterated ethyl acetates were obtained by the low pressure deuteration of vinyl acetate in water-free diethylene glycol dimethyl ether with 5 % Pd on alumina powder
VICINAL
ISOTOPE SHIFTS
49
as catalyst. Partially deuterated vinyl acetates were recovered from the reaction mixture. The deuterated isopropyl groups were obtained by reduction of acetone with LiAlD,. Deuterated acetaldehydes were recovered after deuteration of acetaldehyde with D2 and Pd on Al,O,. Spectra were recorded on a Varian HA-100 spectrometer equipped for deuterium decoupling. The lactate spectra were recorded using time averaging techniques. The preparations of ethyl acetate, lactate, acetaldehyde, vinyl acetate, phycocyanobilin, and methylpheophorbide a contained the full range of the isotopically substituted compounds listed in Table 1. Consequently, the differences in chemical shift due to isotopic substitution could be read directly from a single spectrum. Purification of the various compounds was accomplished by standard techniques of distillation and chromatography. ACKNOWLEDGMENT We thank Mrs. Gail Ryan for recording the spectra.
REFERENCES W. SAUR, H. L. CRESPI, L. HARKNESS, G. NORMAN, AND J. J. KATZ, Anal. Biochem. 22,424 (1968). H. L. CRESPI, S. SKRDLA, AND J. J. KATZ, unpublished. H. BATIZ-HERNANDEZ AND R. A. BERNHEIM, Prog. N.M.R. Spectroscopy 3, 63 (1967). A, L. ALLRED AND W. D. WILK, Chem. Comm. 213 (1969). J. W. MARSMAN, J. LUBACH, AND W. DRENTH, Red. Truv. Chim. Pays-Bus 88, 193 (1969). E. A. HALEVI, Prog. Phys. Org. Chem. 1, 109 (1963). H. L. CRESPI, U. SMITH, AND J. J. KATZ, Biochemistry 7,2232 (1968). J. J. KATZ, R. C. DOUGHERTY, AND L. J. BOUCHER, “The Chlorophylls” (L. P. Vernon and
1. 2. 3. 4. 5. 6. 7. 8.
G. R. Seely, Eds.). Academic Press, New York, 1966.
4
OF
MAGNETIC
RESONANCE
2, 47-49
(1970)
Vi&al Deuterium Isotope Effects on Proton Chemical Shifts* W. SAUR, H. L. CRESPI, AND J. J. KATZ Chemistry
Division,
Argonne
National
Laboratory,
Argonne,
Illinois
60439
ReceivedJuly 31, 1969; acceptedSeptember5, 1969 Vicinal isotope shifts are presented for a number of compounds, including ethyl and isopropyl acetates, lactic acid, and acetaldehyde. Upfield proton chemical shifts of from 0 to 15 x 1O-3ppm per vicinal deuteron are observed. Inverse substitution of 2H for ‘H leads to a remarkably different isotope shift per vicinal deuteron. INTRODUCTION In the course of experiments on the biosynthesis of partially deuterated ethanols (I), lactic acids (2), and other partially deuterated (isotope hybrid) metabolites, we have
observed a number of deuterium isotope effects on the chemical shift of neighboring protons. Of particular interest is the magnitude of some of the vicinal effects, as there appear to be few data on such deuterium isotope effects. A recent review (3) of isotope effects on chemical shifts indicates a need for more experimental observations if deuterium isotope effects on chemical shifts are to be understood. Table 1 lists our results for a number of partially deuterated compounds. These results may be summarized as follows: (1) geminate and vicinal substitution of ‘H by ‘H causes a ‘H upfield chemical shift that is linear with increasing deuterium substitution at equivalent positions; (2) for carbon atoms with tetrahedral geometry, the geminate isotope effect is 15-17 x 10e3 ppm upfield shift per deuteron in a variety of aliphatic and aromatic compounds; (3) for vicinal substitution, the isotope effect on methyl protons results in an upfield shift of 7.2 x 10T3 ppm per deuteron for deuterium substitution at the adjacent methylene or methine group. This value is observed in ethyl acetate, isopropyl acetate, lactic acid, and at the methyl group at position 1 in phycocyanobilin. An upfield shift of 6 x 10V3 ppm is observed in acetaldehyde. However, when the deuterium is substituted into the methyl group of these compounds, a much smaller vicinal effect (0 to 5 ppm per deuteron) on the hydrogen in the methylene or methine position is found. A similar result has been found by Allred and Wilk (4), i.e., (CH3)3CD (isotope shift 9 x 10m3 ppm) and (CD3),CH (isotope shift 1.3 x low3 ppm per deuterium). Marsman, Lubach and Drenth (5) find in acetoin vicinal isotope effects of 8 + 1 x 10m3 ppm in CH,CD(OH)COCH3 and 5 + 1 x low3 ppm in CH2DCH(OH)COCH,. In the ethylidene group at position 2 of phycocyanobilin, the unusually large vicinal effect may be related to the fact that the CHzD group is at the terminum of a highly con* Work performed under the auspicesof the U.S. Atomic Energy Commission. 47
48
SAUR,
DEIJTERIUM
ISOTOPE
CRESPI,
AND
KATZ
TABLE
1
EFFECTS
ON CHEMICAL
SHIFTS
Isotope effect, ppm X 103” Solvent
Conc’n Geminate
CH&HDOCOCH8 CH&D20COCH3 CD$ZH20COCH, CH,CDOHCOOH CHzDCDOHCOOH CHD,CDOHCOOH CHDzCHOHCOOH CDzCHOHCOOH (CD&CHOCH3 (CH&CDOCH, Ar-CH,D Ar-CHD2 CH2=CDOCOCH, CHD=CHOCOCH3 CHzDCHO CH,CDO In phycocyanobilin: Pos. 1: CHa-CD Pos. 2: CHZD-CH=
CCI,
10%
NDCI
0.4 M
Vicinal
16
7 8 5.3 7.4 * 0.3 7.0 * 0.3 7.1 + 0.3 4.3 * 0.3 4.2 & 0.3 4.5 6.5
16.2 f 0.3 16.2 & 0.3
10%
ccl,
Noteb
0.1 M
16.7 i 0.6 16.1 f 0.6
Neat c
cis,
12 Neat c
17
0; tram,
5.0
cis, 0; tram,
13
0
6 Pyridinede
0.1 M
7.2 f 0.5 15 f 2
a All isotope effects listed as per deuterium atom. b These measurements are the average of the four ring methyl groups of phycocyanobilin (in pyridine-d,) and the 1 and 3 methyl groups of methylpheophorbide a (in CDC13). For the structure of the tetrapyrrole compounds, see (7) and (8). c With 50% tetramethylsilane.
jugated system. While our results are consistent with the idea that a deuterium atom is a better electron donor than lH (6), a satisfactory explanation of the nonequivalence of the vicinal isotope effects described here is lacking. As pointed out by Batiz-Hernandez and Bernheim (3) the theoretical explanation of the deuterium isotope effect on proton chemical shifts is in an unsatisfactory state. The isotope shift appears to be the result of small changes in bond length or angle and in contributions from intramolecular electric fields, as well as possible changes in the distribution of molecules over vibrational energy states. Additional data on vicinal isotope shifts should help to delineate the important parameters in the shifts and so to make possible the use of this isotope effect as a tool for the study of molecular structure. EXPERIMENTAL
The partially deuterated lactates were obtained by biosynthesis (2). The partially deuterated ethyl acetates were obtained by the low pressure deuteration of vinyl acetate in water-free diethylene glycol dimethyl ether with 5 % Pd on alumina powder
VICINAL
ISOTOPE SHIFTS
49
as catalyst. Partially deuterated vinyl acetates were recovered from the reaction mixture. The deuterated isopropyl groups were obtained by reduction of acetone with LiAlD,. Deuterated acetaldehydes were recovered after deuteration of acetaldehyde with D2 and Pd on Al,O,. Spectra were recorded on a Varian HA-100 spectrometer equipped for deuterium decoupling. The lactate spectra were recorded using time averaging techniques. The preparations of ethyl acetate, lactate, acetaldehyde, vinyl acetate, phycocyanobilin, and methylpheophorbide a contained the full range of the isotopically substituted compounds listed in Table 1. Consequently, the differences in chemical shift due to isotopic substitution could be read directly from a single spectrum. Purification of the various compounds was accomplished by standard techniques of distillation and chromatography. ACKNOWLEDGMENT We thank Mrs. Gail Ryan for recording the spectra.
REFERENCES W. SAUR, H. L. CRESPI, L. HARKNESS, G. NORMAN, AND J. J. KATZ, Anal. Biochem. 22,424 (1968). H. L. CRESPI, S. SKRDLA, AND J. J. KATZ, unpublished. H. BATIZ-HERNANDEZ AND R. A. BERNHEIM, Prog. N.M.R. Spectroscopy 3, 63 (1967). A, L. ALLRED AND W. D. WILK, Chem. Comm. 213 (1969). J. W. MARSMAN, J. LUBACH, AND W. DRENTH, Red. Truv. Chim. Pays-Bus 88, 193 (1969). E. A. HALEVI, Prog. Phys. Org. Chem. 1, 109 (1963). H. L. CRESPI, U. SMITH, AND J. J. KATZ, Biochemistry 7,2232 (1968). J. J. KATZ, R. C. DOUGHERTY, AND L. J. BOUCHER, “The Chlorophylls” (L. P. Vernon and
1. 2. 3. 4. 5. 6. 7. 8.
G. R. Seely, Eds.). Academic Press, New York, 1966.
4