G. E. MACIEL, P. D. ELLIS,AND D. C. HOFER
2160
Carbon-13 Chemical Shifts of the Carbonyl Group. V.
Observation of a
Deuterium Isotope Effect Using Carbon-13 Field-Frequency Lock112
by Gary E. Maciel, Paul D. Ellis, and Donald C. Hofer Department of Chemistry, University of California, Davis, California (Received December 7, 1966)
An isotope effect of -0.28 ppm on the lSCchemical shift of the carbonyl group in acetone-& with respect to that of acetone has been observed. This result is discussed from a basic vibrational point of view and in the popular language of isotope substituent effects. A useful method for observing lacmagnetic resonance spectra based on a direct lSC fieldfrequency lock system is described.
Introduction Secondary deuterium isotope effects have received considerable attention during the past few years, particularly from the point of view of understanding their basis and their relationship to studies of mechanisms of chemical reactions."6 In addition to the kinetics and equilibrium studies where they are most frequently observed and employed, such effects have been known for some time in proton and fluorine magnetic resonance spectra.'-14 In view of recent demonstrations of a rather sensitive relationship between lacchemical shifts of the carbonyl group and the structural details of the corresponding carbonyl compoundslJ&zO it became of interest to us to learn the influence of a-deuterium substitution on this physical parameter for a representative ketone. Carbonyl'*C shieldings have been studied in some detail both experimentally and theoreticallyz1so that a meaningful interpretation of the results could be anticipated. With the recent development in our laboratories and elsewhere of precise and sensitive 13C magnetic resonance techniques a practical capability exists for the first time for determining small effects such as the expected isotope influences.
Experimental Section Nmr Measurements. The method employed in our experiments used a standard Varian HA-100 spectrometer operating at 23.5 kgauss and 25.1 MHz and a C1024 time-averaging computer which enabled us to record the computer memory from many repetitive frequency-sweep scans. The spectrometer stability The J O U Tof ~Phyeiccrl Chembtry
necessary for effective time averaging was due to a field-frequency control lock signal provided by a capillary (1.2-mm i.d.) containing a W-labeled (55%) material. The field-frequency stability resulting from this simple application of a 13Clock signal from an ex(1) This investigation was supported by a PHS research grant (GM-11439-03)from the National Institute of General Medical Science, U. S. Public Health Service. (2) Paper IV of this series: G. E. Maciel and D. D. Traficante, J. Am. Chem. SOC.,88,220 (1966). (3) E.R. Thornton, Ann. Rev. Phys. Chem., 17, 349 (1966). (4) E.A. Halevi, Progr. Phys. Org. Chem., 1, 109 (1963). (5) E.A. Halevi, M. Nussin, and A. Ron, J. Chem. SOC.,866 (1963). (6) E.A. Halevi and M. Nussin, ibid., 876 (1963). (7) D. D.Traficante and G. E. Maciel, J. Am. Chem. SOC.,87, 4917 (1965). (8) G. V. D. Tiers, ibid., 79, 5585 (1957). (9) G. V. D.Tiers, J. Chem. Phys., 29, 963 (1958). (10) H. Kusumoto, T. Itoh, K. Horota, and J. Ueda, Nippon Seirigaku Zasshi, 15, 728 (1960). (11) T. W. Marshall, Mol. Phys., 4, 61 (1961). (12) H. S. Gutowsky, J. Chem. Phys., 31, 1683 (1959). (13) E.B.Whipple, W. E. Stewart, G. S. Reddy, and J. A. Goldstein, ibid., 34, 2136 (1961). (14) M. Saunders, J. Plostnieks, P. S. Wharton, and H. H. Wasserman, ibid., 32, 317 (1960). (15) J. B. Stothers and P. C. Lauterbur, Can. J. Chem., 42, 1563 (1964). (16) K. 5. Dhami and J. B. Stothers, ibid., 43,498 (1965). (17) K. S. Dhami and J. B. Stothers, ibid., 43, 479 (1965). (18) G. E. Maciel and J. J. Natterstad, J. Chem. Phys., 42, 2752 (1965). (19) G. E. Maciel, ibid., 42, 2746 (1965). (20) G. E. Maciel and G. B. Savitsky, J. Phys. Chem., 68, 437 (1964). (21) J. A. Pople, Mol. Phys., 7, 301 (1964).
CARBON-13 CHEMICAL
SHIFTS OF THE CARBONYL
2161
GROUP
ternal reference is capable of maintaining long-term (several hours) spectrometer resolution of about 1 Hz, with even better results in favorable cases. Methyl alcohol, methyl iodide, carbon disulfide, acetonitrile (methyl labeled), and probably many other simple organic substances furnish adequate lock signals. By employing control-channel modulations up to about 7 kc from an external audio oscillator and judicious combinations of upper and lower side-band control and analytical frequencies the usual range of lSC. chemical shifts can be covered. Thus, the observation of 13C magnetic resonance spectra of natural abundance samples becomes a relatively routine application of the time-averaging technique. Field-sweep experiments with slow sweep rates are also possible, but the lock condition is more fragile. Materials. The l3C-labeled acetone (55% W ) , acetone-& (99% D), and deuterium oxide (99.8% D) were used as obtained from their commercial suppliers, the Isomet Corp., Diaprep Inc., and BioRad Laboratories, respectively.
8
b
I -10
I veffv
Results Using the new technique described in the Experimental Section on a solution containing 5% CHsWOCH3 (55% labeled) and 95% CD3COCD3with lSC present in natural abundance, we obtained a composite frequency-sweep spectrum of the two resonance signals in the carbonyl region. The signal from CHPCOCHa appeared as the expected septuplet resulting from spinspin coupling with the six equivalent protons; the splitting was 6.0 Hz and the line width about 1 Hz. Superimposed on this pattern was a broad peak due to CD313COCD3, centered at an effective frequency22 about 7.0 f 0.5 Hz higher than that of the undeuterated analog. The line width of this broad peak was about 5.0 f 0.5Hz, presumably owing to the envelope of the unresolved 13-line multiplet resulting from splitting by the six equivalent deuterons. Our inability to resolve the individual lines is not surprising in view of the expected 0.9-Hz 13C-C-D spin-spin coupling constant.23 The spectrum of this solution is shown in Figure 1 where it is compared with the spectra obtained from acetone and acetone46 separately. With the available precision of the method and the demonstrated sensitivity of the carbonyl 13C shielding to subtle environmental changes, we compared a lOyo solution of W-labeled acetone in water with an analogous solution in DzO ; with uncertainty limits of about fO.2 Hz we can state that no shift is observed in this case.
I 10
0
HE.
Figure 1. 18C magnetic resonance spectra of acetone and acetone-& on the same scale with the effective frequency v a f i of the center of the acetone multiplet taken as zero. Spectra are frequency sweep and are inverted because of the use of lower sideband detection. A capillary of laCHaOH provided the lock signals: a, CDa’aCOCDs in natural abundance, 120 scans; b, CHalaCOCHa,55% laclabel, one sweep; c, solution consisting of 95% CD&OCDg (with CDPCOCDa present in natural abundance) and 5% CHaWOCH, (55% 1% label), 421 scans.
Discussion Several attempts have been made to understand isotope effects in terms of the vibrational zero-point energies and/or amplitudes on which they depend. Essentially two approaches have been used in this effort: (i) a direct focus of attention on the vibrational phenomena at their origin and (ii) an analysis in terms of “substituent isotope effects.” Within the framework of i, interpretations have been advanced based on an apparently greater inductive electron-donating tendency of D or -C-D compared to H or -C-H and a reduced hyperconjugative ability of -C-D compared to -C-H, i.e., in language appropriate to nonisotopic substituents and classified above as ii. Thus, Halevi416 and eo-workers have presented justification for con(22) The effective frequency, v.ff in Figure 1, is defined for lower side-band operation as the canter-band frequency minus the modulation frequency of the analytical channel. Thia is the frequency at which resonance occurs in a fixed field. (23) This ia given by ( ~ Y H (Jisc) C-H).
Volume 71, Number 7 June 1087
G. E. MACIEL,P. D. ELLIS,AND D. C. HOFER
2162
Table I: Related Isotope Effects 61rC(R1)a
0
-0.28 -1.2
~ ~ P F ( ~ - R c ~ H ~ F ) ~~“F(m-RCsH4F)’
0 -0.01 -0.60
0 0 0
APK,~
&.lWd
0 0.026 0.114
K 0.93K 0.72K
’
a 1% chemical shifts of the carbonyl group with respect to that of acetone from the present work and ref 15. ‘OF chemical shifts of palkylfluorbenzenes from ref 7. ’ IgF chemical shifts of malkyliluorobeneenes from ref 7 . pK,‘s of carboxylic acids relative to that of acetic acid from ref 5. e Relative association constants for the formation of chloranil-alkylbensene complexes from ref 6.
sidering these essentially vibronic phenomena in terms of normal substituent characteristics. Keeping the ultimate vibronic origin in mind, those authors have tried to “correlate secondary deuterium isotope effects in terms of the electrical influences that have proved valuable in interpreting the effects of nonisotopic substituent^"^ and saw no valid objection to regarding deuterium isotope effects as due to small but real differences in the ease of hyperconjugative or inductive electron relezise. Thus “isotope effects on eminently electronic properties” were accounted In the following discussion we consider our results from both of the above points of view. Substituent Isotope Eflects. The result of this work, that a carbonyl carbon attached to two CD3 groups is less shielded by about 0.28 ppm than the carbonyl group in acetone, bears an interesting relationship to some previous work as exhibited in Table I. One sees no correspondence between the lac carbonyl shieldings and the 19Fchemical shifts of the rn-fluoroalkylbenzenes for which an “inductive isotope effect” was not found. Trends in the same direction are noted between the 13C carbonyl shieldings and the I9F shieldings in p-fluoroalkylbenzenes and might be discussed in terms of hyperconjugative effects; however, the ratio of increments corresponding to given substituent changes is not at all comparable for these two series of data. A qualitatively more attractive trend is observed between the carbonyl-lac shieldings and the equilibrium constants for the association of chloranil and ethylbenzene, with toluene, toluene-a,a, CY-&, which Halevi and Nussin have interpreted primarily in terms of the hyperconjugative abilities of CH3, CDa, and C2.&,. This comparison can also be made in the table. Thus, the present data could be rationalized in terms of hyperconjugative influences if one is willing to view these problems from the point of view of “substituent isotope effects.” However, in that event, one niust note that in the ketone series CH3”COCHa, CDPCOCD3, C2H61aCOC&, the effect on the 13C shielding of replacing CHa by CD3 is roughly the same frrtction of the effect of replacing CHI by The Journal of Physical Chemistry
C2Hb as the corresponding ratio of APKA’Sin the series of acids5 CHaC02H, CD3C02H, and C~H~COZH, which are structurally more closely related to the ketones than are the alkylbenzenes. Since the results on the carboxylic acids, shown in Table I, were assumed by Halevi to reflect a dominant role of an inductive effect, one might therefore conclude that the order of carb~nyl-’~C shieldings is due to substituent inductive and isotopic inductive effects. This would be consistent with the interpretations of Stothers and LauterburlSand Maciellg that inductive withdrawal by a substituent depolarizes the carbonyl ?r bond, thereby increasing the shielding of the carbonyl-13C nucleus. This relationship has been put in quantitative terms by an application to the case of carbonyl systemslg of the independent electron molecular orbital theory for carbon-13 chemical shifts formulated by KarplusZ4 and P ~ p l e . ~ ’This , ~ ~ treatmentlg expresses the dominant paramagnetic term for 13C carbonyl shielding by eq 1, where X has the usual meaning of ?r-bond poqpAA=
-(296
+ 95.7X)[l + 0.273(1 - X2)’/’]
(1)
l a r i t ~ . For ~ ~ a range of X between 0 and about 0.7 this expression predicts a nearly linear dependence of the carbon shielding on the bond polarity parameter and has been useful in interpreting both inductive substituent and solvent effects on carbonyl shieldings. The present data could be interpreted in “substituent effect” language in terms of eq 1 if one assumes that the order of inductive electron-withdrawing ability is CH3 > CD3 > C2H6as in Halevi’s carboxylic acid PKA interpretation5 and that X thereby decreases in that order. Unfortunately, the effect of conjugating or hyperconjugating substituents attached to carbonyl groups on their 13C chemical shifts has been obscured by the lack of an effective means of correcting for the “neighbor anisotropy effect.”’g Thus, it is not possible at (24) M. Karplus and J. A. Pople, J . Chem. Phys., 38, 2803 (1963).
(25) The definition of X is given by the expression for a localized n-bond orbital $ = [(l X)/2]1/*@pr~ [(l X)/2I1/~@p,o.
-
+
+
CARBON-13 CHEMICAL SHIFTS O F THE CARBONYL GROUP
this time to predict with even qualitative certainty the hyperconjugative influence in carbonyl systems. It is of relatively little help to compare directly the influences of alkoxy or amino groups on carbonyl-13C shieldings; those substituents, while exerting electrondonating conjugation effects, simultaneously exert electron-withdrawing inductive influences on the carbonyl group and one can rationalize the resulting relatively high shieldings on the latter basis. Reference to the related 1 7 0 data is somewhat more helpful. Indeed, the available 170 carbonyl chemical shifts26 (with respect t o H2170) for acetone (-572 ppm), 3-pentanone (-548 ppm), ethyl acetate (-356 ppm), and acetamide (-286 ppm) seem to reflect primarily the mesomeric electron-donating ability of the methoxy and amino groups compared t o alkyl groups attached to the carbonyl. Neglecting the neighbor anisotropy effects of the alkyl groups on the 170shielding and assuming that an expression analogous to eq 1 applies, the position of 3-pentanone in this series would seem to indicate that either CHI is more inductively withdrawing (or less inductively donating) or else it is less electron donating in a hyperconjugative sense than is CzH5. Since the latter alternative is contrary t o the usual interpretation of hyperconjugative effects it would seem more plausible to ascribe the order t o the relative inductive effects of the methyl and ethyl groups. If this is a valid indication of the influence which these substituents exert on the polarity parameter A, then one would expect a corresponding influence in the opposite sense on the l3C shielding in the carbonyl. A relationship of this type based on a mutual dependence on X has been demonstrated previously for the case of solvent effects on the 13C and 170chemical shifts of acetone in a variety of solvents in which X varies; this correlation is shown in Figure 2. Thus, the present data can, in the language of “isotope substituent effects,” be interpreted most reasonably as demonstrating the following decreasing order of inductive withdrawing ability: CH3 > CD3 > CzHs. However, for reasons to be discussed in the next section this general type of view (ii above) should be employed only with careful reference to the more fundamental vibrational foundation and not without caution. Vibronic Point of View. The previously mentioned investigation of isotope effects in fluorotoluenes has been viewed by Thornton as “about as close as one can hope to get t o isolating purely electronic effects from the average vibrational effects.” In that case the isotope effects on the 19F chemical shifts were found t o be much smaller than one might have estimated by comparison of isotope and substituent effects on chemical reactivity parameters and a considera-
2163
10
5
.o
i=
6 Lo
b
-5
. -10 I
1
I
I
-1
-2
I
0 6%,
ppm.
Figure 2. Plot of carbonyl chemical shift of acetone in solvents at 1:1 volume ratio us. the ”0 chemical shift in the same solvents a t the same concentration. Data from ref 27 and 28.
tion of substituent effects on lgF shieldings in substituted benzenes. Now, in the present case the effects on the 13C carbonyl shielding of replacing a methyl group by a perdeuteriomethyl group or an ethyl group are in roughly the same proportions as such structural changes on the cited reactivity parameters. However, this does not mean that the present results on isotopic substitution should be interpreted as representing electronic effects in the usual sense. That is, the present results do not suggest a case for which the Born-Oppenheimer approximation is invalid. Such an invalidation would require different potential energy surfaces describing the potential energy functions of nuclear motion for the isotopically related molecules. This surface, in the Born-Oppenheimer approximation, results from solving the electronic Schrodinger equation as a function of the coordinates describing internuclear separations and must be essentially identical for isotopic isomers, leading to identical force constants for molecular vibrations. As emphasized by Thornton this is an entirely different case from that of comparing different compounds; even for closely related homologs different potential energy surfaces and consequently different force con~~
(26) H. A. Chrust, P. Diehl, H. R. Sohneider, and H. Dahn, Helv. Chim. Ada, 44, 865 (1961).
(27) J. J. Natterstad, M.S. Dissertation, University of California, Davis, Calif., 1965. (28) H. A. Christ and P. Diehl, Xelv. Phys. Acta, 36, 170 (1963).
Volume 71, Number 7 June 1067
G. E. MACIEL, P. D. ELLIS,AND D. C . HOFER
2164
stants and molecular geometries apply. Thus, the effects of isotopic substitution result entirely from changes in the details of nuclear motion and, unlike the case with molecules which differ by more than just isotopic substitution, are not related to or dependent on different potential energy surfaces, i.e., on different parametric solutions to different parametric electronic Schrodinger equations. Because of this fundamental difference cautious restraint should be exercised in discussing isotope effects in the language of substituent effects. With this in mind, it appears that the most useful and proper interpretation of the present results is simply based on the fact that, although the force constants for vibrations in acetone and acetone-& are essentially identical, the mass differences of H and D result in differences in vibrational amplitudes and different “effective” molecular geometries. If the molecular vibrations are anharmonic, then different vibration amplitudes will result in different mean bond distances for the isotopically related molecules. This means that one must, in principle, solve two slightly different electronic Schrodinger equations to describe the electronic properties, such as the electronic shielding constant of the molecules. In a sense this amounts to a different choice of the nuclear orientation index X in Ramsey’s original formulation of the theory of magnetic shielding of nuclei in molecules.29 These same ideas have been presented in a useful form by Marshall” in a theoretical consideration of isotope shifts in the nmr spectra of Hz, HD, and Dz. He has expressed the “center of gravity” of a resonance line as corresponding to a value of the shielding constant u averaged over nuclear motion (Tobsd
= lqzUm
(2)
where R is the value of the internuclear separation and * ( R ) is the wave function describing nuclear motion. Then, expressing u as an expansion in the neighborhood of Re, the equilibrium internuclear separation, Marshall obtains
u(R) ‘Jobsd
=
=
+ (R - Re)u’(Re) + ‘ / z ( R- RJ2g”(Re) u(Re) + u’(Re)fqz(R- R e ) U u(Re)
(3)
1/2r”(Re)f\E2(R- RJ2dR (4) where u(Re) is the shielding corresponding to the equilibrium configuration (bottom of the potential energy
The Journal of Physical Chemistry
curve) and the primed symbols refer to derivatives. Analogous polydimensional expressions would apply to the laccarbonyl shielding in acetone. According to eq 4 only two distinct effects need be considered for isotopic effects (the first term on the right is the same for isotopic isomers since the potential energy curves or surfaces are essentially identical). The second term on the right is nonzero if the potential energy curve or surface has an anharmonic part so that the average internuclear configuration differs from Re; in this case f+2(R - Re)d.R will depend on the isotope, owing to the differences in vibrational amplitudes. This effect has been mentioned above. The third term on the right also depends on the amplitudes of vibration, but it is nonvanishing even in the event of a purely harmonic potential function; this will also contribute to an isotope effect on shielding. Thus, the present data can, within the framework of the BornOppenheimer approximation, be interpreted as a demonstration of the effect of isotopic substitution on the effective geometry of the acetone molecule, resulting in slightly different effective electronic properties such as magnetic shielding; this is conceptually associated with the hypothetical solution of the electronic problem corresponding to slightly different spatial configurations of the nuclei. There is an apparent contrast in the results with the acetones of this work and the fluoroalkylbenzenes previously reported; in the latter case isotope effects on the l g F shieldings did not reflect the magnitudes observed in isotope effects on superficially analogous chemical properties, while in the former case the lac shieldings appear to be more directly related to chemical results. The reason for this is presumably that those aspects of the molecular electronic wave function of the acetone molecule in a magnetic field which determine the magnetic shielding of its carbonyl carbon are more profoundly influenced upon deuterium substitution in methyl groups by the changes in the “effective” spatial orientation of the nuclei (i.e., by changes from one portion of the potential energy surface to another) than are the corresponding factors determining ‘9F shieldings in fluoroalkylbenzenes. This is most likely related to the relative proximity of the position of deuterium substitution and the magnetic nuclei of interest in the two cases. In this regard it is of interest to note that the relatively huge isotope effect of 3 ppm has been reported for the difference between the 1 7 0 chemical shifts in DzO and Hz0.z6 (29)
N. F. Ramsey, Phys. Rev.,
78, 699 (1950).
