J . Phys. Chem. 1990, 94, 6679-6683
6679
Proton NMR Studies of Symmetrically Substituted N,N-Dialkyltrifluoroacetamides: Medium Effects Cristina Suarez, Clifford B. LeMaster, Carole L. LeMaster, Mohsen Tafazzoli, and Nancy S. True* Department of Chemistry, University of California, Davis, California 95616 (Received: February 15, 1990)
Activation parameters characterizing the internal rotation about the C-N partial double bond in a series of symmetrically N,N-disubstituted trifluoroacetamides (CF3CON(R),; R = ethyl, isopropyl, and isobutyl) have been determined from exchange-broadened'HNMR spectra. Gibbs energies of activation, AC*29s(kcal mol-'), are for the gaseous trifluoroacetamides and their 1% CCI4 solutions as follows: diethyl, 16.1 (0.1)/17.8 (0.1); diisopropyl, 15.8 (0.1)/16.3 (0.1); diisobutyl, 16.4 (0.1)/17.3 (0.1). In both the gas and liquid phases rotational barriers decrease with increasing N-alkyl substituent bulk. The phase dependence of these parameters is compatible with expected solvent internal pressure effects. Lower gas-phase activation energies are consistent with a process proceeding via a transition state that has greater steric requirements than the ground-state configuration.
Introduction
are lower than in the liquid. This further lowers the temperature at coalescence for the gas compared to the liquid. While the acetamides suffer from all these difficulties, the trifluoroacetamides studied have vapor pressures ranging from 1.8 to 2.4 Torr at 298 K, greater than the corresponding formamides and acetamides, from three to nine magnetically equivalent protons, and adequate-to-large gas-phase limiting chemical shift differences (DMTFA 0.098 ppm/49 H z ; ~DETFA methyl resonance 0.034 ppm/l7 Hz; DIPTFA methyl resonance 0.151 ppm/75.6 Hz; DIBTFA methylene resonance 0.035 ppm/l1 Hz; all separations in hertz are at 500 MHz except for DIBTFA, which is at 300 MHz). These properties make the trifluoroacetamide series one of the most ideal amide series for gas-phase study. Gas phase AG% for internal rotation in amides have invariably proven to be lower than those in liquid phase^.^-^ This difference may be attributed to solvent or other intermolecular effects in liquids that preferentially favor the ground-state molecule over the transition state. These effects may be either dielectric or steric in nature. Dielectric effects for the alkyl-substituted trifluoroacetamides are expected to be similar, allowing the magnitude of the steric contribution to be determined. This contribution can be modeled by considering solvent internal pressure effects that arise from local packing and cohesive forces. For conformational isomerization processes, the change in free energy of activation with respect to pressure at constant temperature is equal to the activation volume, AV, for the process:8
Variable-temperature N M R spectroscopy has assumed a primary role in the study of conformational exchange kinetics of amides.lS2 In the past, most of these studies have been restricted to liquid samples. However, extension of the N M R method to gaseous amides has allowed the determination of solvent and medium effects on conformational processes by mean of a direct comparison between gas-phase and solution results obtained by using the same experimental t e c h n i q ~ e . ~ -In ~ this article the differences between the gas-phase and solution Gibbs energies of activation characterizing the internal rotation about the C-H amide bond in a series of N,N-symmetrically substituted amides (diethyl- (DETFA), diisopropyl- (DIPTFA) and diisobutyltrifluoroacetamides (DIBTFA)) are discussed in terms of molecular steric requirements in condensed phases. Previously obtained values for N,N-dimethyltrifluoroacetamide(DMTFA) are reconsidered in light of this new information. The determination of gas-phase amide rotational barriers suffers from several difficulties. First, available vapor pressure is extremely low, usually below I Torr at 298 K. While this does not preclude study if there is sufficient magnetic equivalence of the protons and minimal splitting of peaks by coupling, it certainly limits the low end of the attainable temperature range, often making the accurate slow-exchange parameters required for line-shape analysis unobtainable. Under these circumstances, these parameters must be estimated, and although the free energies of activation are still fairly reliable, enthalpies and entropies of activation usually become meaningless. Second, limiting chemical shift differences (Aa) between conformers are often smaller in the gas phase than in solution, and sometimes, in the extreme, the conformers become indistinguishable due to isotropy of their proton environments. For instance, the gas-phase Aa's for N,Ndimethylformamide,s propionamide, and butyramide are zero and for N,N-dimethylacetamide, 0.047 ppm! although the liquids show splittings of 0.17 (IO vol 7% in CC14),50.15 (neat), 0.22 (neat), and 0. I8 ppm (neat), respectively. A small limiting chemical shift difference lowers the coalescence temperature, a disturbing effect when dealing with low vapor pressure compounds. Last, the rotational barriers of all the amides so far studied in the gas phase
[dAG*/dPIT= AV (1) For ideal gases the internal pressure is zero; internal pressures in typical liquid solvents range from 2000 to over 20000 atm in H20.9 For a typical dimethylamide undergoing internal rotation, the activation volume is 15 cm3 m01-I;~thus, the internal solvent pressure effect can cause medium-dependent variations in AG* for conformer interconversion in the range 0.7-7 kcal mol-' based solely on steric factors. The size of the substituents on the amino nitrogen atom will change the steric contribution to the activation volume. Previous liquid studies, which measured exchange rates as a function of applied external pressure, have reported that AV's in N,N-disubstituted benzamides decrease with increasing substituent size (dimethyl = 8.6 cm3 mol-', diethyl = 7.7 cm3 mol-', and diisopropyl .= 5.4 cm3 mol-').'o Studies of this series of trifluoroacetamides should help determine the relative contribution of steric and dielectric effects to the observed LIP'S. If steric effects predominate, a decrease in gas to liquid differences in AG* will
-
( 1 ) Stewart, W. E.: Siddall, T. H. 111 Cfiem. Rev. 1970, 70, 517-551. (2) Jackman, L. M. In Dynamic Nuclear Magnetic Resonance Spectroscopy; Jackman, L. M., Cotton, F. A,, Eds.; Academic Press: New York, 1975: Chapter 7, pp 203-252 and references therein. (3) Fiegel, M. J. Pfiys. Chem. 1983, 87, 3054-3058. (4) Ross. 9. D.: Wong, L. T.:True, N. S. J. Pfiys. Cfiem. 1985, 89,
836-839. ( 5 ) Ross, 9. D.; True, N. S. J. Am. Chem. Soc. 1984, 106, 2451-2452. (6) Ross, 9. D.: True, N. S.; Decker, D. L. J. Pfiys. Cfiem.1983,87,89-94. ( 7 ) LeMaster, C. 9.; True, N. S . J . Pfiys. Cfiem. 1989, 93, 1307-1311.
0022-3654/90/ 2094-6679$02.50/0
(8) Chandler, D. J. G e m . Pfiys. 1978, 68, 2959-2970. (9) Dack, M. R. J. Cfiem. Soc. Rev. 1975, 4 , 211-229. (IO) Hauer, J.: Volkel, G.: Liidemann, H.-D. J . Cfiem.Res., Symp. 1980, 16-17. 1
1990 American Chemical Society
6680 The Journal of Physical Chemistry, Vol. 94, No. 1 7 , 1990 occur as the substituent size increases. In contrast, if dielectric effects are most important, AV's will be similar regardless of the size of the substituents. Dielectric effects are due to the reduced polarity of the transition-state versus the ground-state configuration. Experimental Section
The N,N-disubstituted trifluoroacetamides were synthesized by dropwise addition of trifluoroacetic anhydride (Aldrich Chemical Co.) to the appropriate amine: diethyl, diisopropyl or diisobutyl (Aldrich Chemical Co.). An excess (3:l mol ratio) of the amine was used to ensure complete reaction of the anhydride. The reaction was carried out at 0 "C with constant stirring. The products were purified by direct distillation followed by vacuum distillation and characterized by their ' H N M R spectra. Gas-phase NMR samples were prepared in Wilmad, highprecision NMR tubes. The sample-handling techniques and vacuum system used in their preparation have been previously described." The DETFA sample was prepared in a 5-mm NMR tube which contained 0.5 Torr of DETFA, 0.5 Torr of T M S (Aldrich), and 300 Torr of argon (Matheson Gas Co.). The DIPTFA and DIBTFA samples were prepared in 12-mm insert tubes and contained 1.8 Torr of DIPTFA/ 1 .O Torr of TMS/300 Torr of SF6 and 0.2 Torr of DIBTFA/O.l Torr of TMS/410 Torr of SF6, respectively. Due to high vibrational-state density in the temperature range of study, rates of conformational processes in amides are not pressure dependent at pressures above a few Torr." Liquid samples of all the amides studied were prepared in 5-mm NMR tubes and contained 1% by mole amide in CCI.,. Both the amide and the solvent were degassed by three successive freezepump-thaw cycles prior to sample preparation. ' H NMR measurements for gaseous DETFA and liquid DIBTFA were performed on a Nicolet 11.8-T spectrometer ('H observation at 499.92 MHz) equipped with a Bradley 5-mm proton probe. All measurements were made on spinning samples in the unlocked mode. Acquisition times for gas-phase DETFA spectra were 0.34 s/transient with a pulse angle of 87O ( 1 3 ps) and a delay time of 0.5 s. Short delay times are typical of gas-phase NMR due to short relaxation times. Typically, 1500-2000 transients were collected at each temperature, stored in 8K (double precision) of memory, and zero-tilled to 8K (single precision) prior to Fourier transformation. A sweep width of f3012 Hz was used for all spectra, giving a digital resolution of 0.73 Hz/point after zerofilling. The resulting trifluoroacetamide spectra had typical signal-to-noise (S/N) ratios of 1O:l (slow exchange) and 40:l (exchange). For liquid DlBTFA spectra, typically 100 transients were collected with a 2 . 0 5 s acquisition time, a 5-s delay time, and a pulse angle of 27O (4 ps). Digital resolution of 0.24 Hz/point was obtained with a sweep width of f 2 0 0 0 Hz. The spectra were stored in 16K of memory prior to Fourier transformation and had signal-to-noise ratios of at least 100:l. Exchange-region spectra were multiplied by an exponential linebroadening factor of 1 .O Hz to increase S/N. No exponential line-broadening was used for slow-exchange spectra to achieve maximum resolution of coupling constants. A 500-MHz spectrometer was used for these compounds to increase the limiting chemical shift difference between the conformers and thus expand the temperature region of study. Gaseous DIBTFA and DIPTFA and liquid DlPTFA and DETFA spectra were acquired on a General Electric NT-300 spectrometer ('H observation at 300.07 MHz) equipped with a Bradley 12-mm proton probe using spinning samples in unlocked mode. Acquisition parameters for the gases were identical with those for gaseous DETFA, except that typically IO00 transients were collected at each temperature. Characteristic resulting spectra have S / N ratios of about 75:l. The 300-MHz spectrometer was used for these compounds because of its wider bore size, allowing use of a 12-mm probe that dramatically increases S / N due to the increased number of molecules in the active volume. ( I I ) Ross. B. D.: True, N . S . J . A m . Chem. Six. 1983, 105. 4871-4875.
Suarez et al. TABLE I: Gas- and Liquid-Phase Activation Energies at 298 K for Internal Rotation in N,N-Dialkyltrifluoroacetamides AGlgas, AG',iq, PAG', kcal mol" kcal mol-' kcal/mol-' 16.5 (O.l)a 18.1' I .6 DMTFA DETFA 16.1 (0.1) 17.8 (0.2) 1.7 DlPTFA 15.8 (0.1) 16.3 (0.1) 0.5 DIBTFA 16.4 (0.1) 17.3 (0.1) 0.9 QCalculated from rates in ref 6. *Reference 17, 11.25 mol % in CCI&
TABLE 11: Gas- and Liquid-Phase Limiting 'H Chemical Shift Differences in oom for N.N-Dialkvltrifluoroacetamides N-C-H N-C-C-H aas lia' AAu aas lia PAu DMTFA 0.098' 0.1 15' -0.017 0.012 0.047 -0.350 DETFA 0.035 0.065 -0.030 DIPTFA 0.265 0.163 0.102 0.848 0.680 0.168 DIBTFA 0.034 0.056 -0.022 -0 -0 -0 Liquid values are 1 mol % amide in CC14. *Reference 6.
Acquisition times for the DlPTFA and DETFA liquid-phase spectra were 3.85 s/transient with a pulse angle of 1 O ( 1 5 ps) and a delay time of 5.0 s. Typically, 48 transients were collected at each temperature and stored in 16K (single precision) of memory. The resulting spectra have S / N ratios >75:1 at slow exchange and >500:1 during exchange for the methyl peaks studied. A sweep width of 11064 Hz was used, giving a digital resolution of 0.26 Hz/point. Probe temperature was measured and the gradient evaluated prior to each gas-phase acquisition by using three copperconstantan thermocouples placed at different heights within a spinning NMR tube in the active volume. Temperature within the active volume of the probe was found to be constant to within 0.1 K in the 5-mm probe and to within 0.2 K in the 12-mm probe. Temperatures in liquid samples showed no gradient within the active volume. Prior to spectral acquisition gas-phase samples were allowed to equilibrate for 10 min at each temperature, and liquid samples were allowed to equilibrate for 30 min. Rates were analyzed by using the line-shape analysis program D N M R S . ' ~ A linear temperature dependence was assumed for estimation of the natural line widths at each exchange temperature, where the T M S line width represented an estimate of the field inhomogeneity. The gas-phase DETFA methyl peak ha used for line-shape analysis showed a probable very small dependence on temperature. The temperature range at which slow-exchange spectra could be run for DETFA (262-272 K; the spectra showed probable exchange broadening above 262 K) precluded any characterization of the dependence. If a chemical shift dependence on temperature appeared likely for any amide, shifts were allowed to vary in the iterative line-shape analysis. Coupling constants showed no dependence on temperature for any of the amides studied. Liquid T2 values were obtained as for the gases, except, due to limitations caused by the boiling point of the solvent of choice, CCI4, only slow-exchange spectra were obtained. Slow-exchange spectra were obtained from 258 to 283 K. These spectra were also used to estimate the temperature dependence of the limiting chemical shifts. N
Results Comparison of the gas-phase and solution results indicates considerable medium effects on A@. Table I lists the free activation energies for the gaseous amides and for their 1 mol % solutions in CCI,, and Table I1 shows the phase dependence of the limiting chemical shift differences (uncertainties in chemical shift values are ca. f 0 . 0 0 2 ppm; coupling constants carry un(12) (a) Stephenson, D. S.; Binsch, G. Program 365. (b) LeMaster, C . B.; LeMaster, C . L.; True, N . S. Programs No. 569 and QCMP059; Quantum Chemistry Program Exchange, Indiana University, Bloomington. IN 47405.
Symmetrically Substituted N,N-Dialkyltrifluoroacetamides
-0’5 -1.0 A
5-
-1.5
W
C
1
-2.0 -2.5
A A
A
A
A
A
1
I J
-4.0 -4.5
1
A A
322.7 @ K
0 A
e
e
m
* A
A
m U
e
I
2.80
2.90
I
I
I
I
I
3.00
3.10
3.20
3.30
3.40
1000/T Figure 1 . Eyring plot of gas- and liquid-phase exchange rate constants for disubstituted trifluoroacetamides: 0, DETFA gas; A, DIPTFA gas; 0,DIBTFA gas; 0 , DETFA liquid; A, DIPTFA liquid; DIBTFA
.,
liquid.
TABLE 111: Rate Constants (k)for Internal Rotation in DETFA
T, K 308.1 31 1.8 3 14.7 317.2 320.2 321.9 322.7 331.5 334.5 336.9 340.4 343.3 346.0 349.8
A
385.0 K
1
-3.5
The Journal of Physical Chemistry, Vol. 94, No. 17, 1990 6681
ksas. s-’ 22.6 (2.1) 33.3 (1.7) 48.5 (4.5) 54.3 (3.4) 63.0 (8.3)
ki,,,
I310
I300
570
540
510
HZ
Figure 2. Temperature-dependent gas-phase 500-MHz IH N M R spectra of DETFA from I .26 to I .02 ppm (referenced to gaseous TMS, 0.00 ppm) showing exchange broadening of the methyl proton resonances. From top to bottom, line shapes represent the calculated and experimental spectra at the indicated temperature. Associated exchange rates appear in Table 111. TABLE IV: Rate Constants for Internal Rotation in DIPTFA and DIBTFA
DIPTFA
5.1 (0.3) 75.0 (5.4) 9.9 (0.5) 11.9 (0.6) 15.0 (0.8) 19.9 ( 1 . 1 ) 29.5 (2.2) 33.8 (2.1) 40.4 (2.3)
certainties on the order of ca. f0.1 Hz). Rate constants for the amides appear in Tables 111 and IV, and Eyring plots of these rate constants appear in Figure I . Specific observations and kinetic data for each molecule are described below. N,N-Diethyltrifuoroacetamide. At 278 K, the gas-phase IH methyl resonances appear in the spectrum at 1.198 and 1.163 ppm downfield from gaseous TMS, separated by 17.5 Hz (0.035 ppm) in a 11.8-T field. This separation allowed six rate constants to be obtained at temperatures between 308.1 and 322.7 K. The methylene resonances appear at 3.459 and 3.447 ppm (Au = 0.012 ppm). The 3 J H H coupling constants for the two ethyl groups were 7.0 Hz, equal within experimental error. Only the methyl resonances were used in the line-shape analyses because of the smaller Au of the methylene resonances. Coupling with fluorine was not observed in the gas-phase spectra. Figure 2 shows temperature-dependent gas-phase proton spectra of DETFA. At 249.0 K, the IH methyl resonances for a 1 mol % solution in CCll appear at 1.293 and 1.221 ppm ( A u = 0.072 ppm) and the methylene resonances at 3.467 and 3.449 ppm (Au = 0.018 ppm). Coupling with fluorine was not resolved in the spectra, but the downfield peaks of each set were broadened relative to the upfield peaks indicating they are cis to CF,; thus, the resonances at 1.293 and 3.467 ppm are assigned to the conformer trans to the carbonyl in agreement with the assignment of Graham.I3 Coupling constants, 3 5 H H , are 7.0 (trans to carbonyl) and 7.1 Hz (cis to carbonyl). Eight rate constants were obtained between 321.9 and 349.8 K by analyzing the band shape of the ex(13) Graham, L. Org. Magn. Reson. 1972, 4(2), 335-342
T, K 294.8 299.1 303.3 304.8 307.2 307.4 310.4 311.8 3 13.2 3 14.8 316.1 317.6 319.0 321.1 321.8 323.9 324.6 326.8 327.8 330.2 330.7 333.2 333.4 336.2 338.0 339.1 342.8
kgas,s-’ 10.9 (0.6) 18.5 (1.1) 29.0 (2.3) 42.6 (2.9) 59.4 (3.2) 72.8 (4.1) 91.6 (4.9) 119.3 (6.3) 154.9 (8.2) 187.0 (10)
DIBTFA T, K 299.1 303.4 308.0 13.0 (0.8) 31 1.0 314.1 16.0 (0.9) 319.6 19.9 ( 1 . 1 ) 320.5 322.8 25.2 (1.4) 323.2 326.0 30.3 (1.8) 328.8 33 1.4 37.0 (2.2) 334.0 338.0 45.1 (2.5) 340.0 342.0 54.9 (3.0) 346.6 351.1 66.4 (3.5) kii,, s-’
kgarrS-’ 6.4 (0.8) 9.7 ( 1 .O) 15.1 ( 1 . 1 ) 18.9 (1.6) 24.6 (2.0) 42.2 (2.3)
kii,, s-’
9.4 (0.8) 52.8 (2.6) 11.3 (0.6) 15.7 (1.0) 18.4 ( 1 .O) 21.7 (1.3) 28.3 (1.9) 38.5 (2.2) 44.5 (2.4) 49.3 (2.5) 67.8 (3.6) 97.4 (5.0)
232.0 ( I 3) 86.4 (4.6) 287.0 ( 1 6) 104.5 (5.5) 124.6 (6.7) 405.0 (63) 148.6 (7.8) 525.0 (82)
change-broadened methylene resonances. N,N-Diisopropyltrijluoroacetamide.At 216.4 K,the gas-phase ‘ H methyl resonances appear in the spectrum at 1.447 and 1.212 ppm downfield from gaseous TMS, separated by 75.6 Hz (0.265 ppm) in a 7.05-T field, allowing 14 rate constants to be obtained at temperatures between 294.8 and 342.8 K. The methine resonances appear at 4.320 and 3.472 ppm (Au = 0.848 ppm). The coupling constants, ,J,+H, for the two conformers are 6.5 (upfield methyl) and 6.6 H z (downfield methyl). Only the methyl resonances were used in the line-shape analyses because of the low S/N of the methine resonances. Coupling with fluorine was not
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The Journal of Physical Chemistry, Vol. 94. No. 17, 1990
TABLE V: Summary of Free Activation Energies (298 K) and Activation Volume Calculations for Disubstituted Amides (R,CONR,R3 R,
R2
C F; C F,
e
18.1' 17.8 (0.1) 16.3 (0.1) 17.3 (0.1) 20.7g 20.4' 20.71 18.2' 17.71 16.2'
AG*l,q- Actgas (experimental) in kcal mol-l. b A p in cml mol-]. AG*l,qReference I7 /Reference 5. Reference 1 8 Reference 7 ' Reference 19.
observed in the gas-phase spectra. At 258.5 K, the ' H methyl resonances for a 1 mol % solution in CCI, appear at 1.414 (cis to carbonyl) and 1.255 ppm (trans, Po.= 0.1 59 ppm) and the methylene resonances at 4.148 (trans) and 3.475 ppm (cis, ACT= 0.673 ppm), both having smaller Pu's than the gas phase. Eleven rate constants were obtained at temperatures between 320.5 and 351 . I K from the band-shape analysis of the exchange-broadened methylene resonances. Coupling with fluorine was not resolved, but the downfield methine peak is broader than the corresponding upfield peak, indicating protons that are cis to CF, (trans to carbonyl). Coupling constants, 'JI;(,+ are 6.6 (trans to carbonyl) and 6.8 Hz (cis to carbonyl). Fluorine and proton coupling constants were used for the peak assignment, which is consistent with the previous assignment of Graham.I3 N,N-Diisohutyltrifluoroacetamide. At 246.2 K, the gas-phase 'H methylene resonances appear in the spectrum at 3.336 and 3.301 ppm downfield from gaseous TMS, separated by 10.6 Hz (0.035 ppm) in a 7.05-T field, allowing seven rate constants to be obtained at temperatures between 299.1 and 322.8 K. The for the two conformers are both 6.7 Hz; coupling constants, ,JHH, again, coupling with fluorine was not observed in the gas-phase spectra. As with DIPTFA only the methylene resonances were used in the line-shape analyses because of the low S / N for the methine resonances and the negligible difference in limiting chemical shifts of the methyl peaks. At 258.2 K, the ' H methylene resonances for a 1 mol % solution in CCI, appear at 3.246 (cis to carbonyl) and 3.192 ppm (trans), La = 0.054 ppm) and the methine resonances at -2.027 ppm (cis and trans unresolved), the methylenes having smaller Aa's than in the gas phase. Coupling with fluorine was not resolved, but the downfield methine peak is broader than the corresponding upfield peak, indicating protons that are cis to CF, (trans to are both 7.8 Hz. Peak carbonyl). Coupling constants, ,JHH, assignments, which are consistent with the previous assignments of Graham,', were made by using the fluorine and proton coupling cons tan ts.
Discussion Table V summarizes the data obtained in this study as well as similar data available for acetamides and formamides. The two most obvious results of this study are the observed decrease in the amide rotational barrer as the substituents on the nitrogen atom increase in bulk and the higher gas-phase exchange rate constants and lower free activation energies versus liquids. Two other interesting observations are the lower gas-phase proton limiting chemical shift differences in all the substituted trifluoroacetamides studied, except DIPTFA, and the relative barrier heights of the trifluoroacetamides versus the acetamides. These results will be discussed below. The introduction of conformationally mobile alkyl groups into the amide framework affects the magnitude of the internal rotational barrier about the C-N partial double bond. In this trifluoroacetamide series, replacement in the gas phase of the methyl substituents by ethyl decreases the barrier from 16.5 to 16.1 kcal mol-'; isopropyl replacement causes a further decrease to 15.8 kcal mol-': isobutyl substitution decreases the barrier to
CCI, CCl4 CCI, CCI, c2c14
neat 0-DCB neat O-DCB 0-DCB
1.6 1.7 0.5 0.9 I .3 1.2 1.7 2.5
15 20/18 12 II 15 16 4 15
1.8
12
1.1 l.S/l 0.9 0.8 1.1 2.2 0.4 2. I I .2
in kcal mol-' from eq 1 using calculated AV*. dReference 6 . Reference 20. Reference 4. 'Reference 21. Reference 5.
16.4 kcal mol-'. A similar trend is observed in the liquid. This observation has been explained previously2as resulting from steric effects on the ground-state molecule. The large substituent groups force the molecule out of its preferred planar configuration, lessening the sp2 character of the C-N bond. The decrease in double-bond character lowers the rotational barrier about this bond. The trend is apparent in both the liquid and gaseous amides, the most notable difference being the larger decrease in AG* between the N,N-diethyl- and N,N-diisopropyl-substitutedmolecules in the liquid versus the gas phase. The difference may be due to the fairly dramatic decrease in activation volume for diisopropyl versus diethyl substitution. The magnitude of the rotational barrier appears to depend primarily on the number of substituents on the carbons directly bonded to the nitrogen because increasing bulk at this position results in destabilization of the ground state. Replacement of the isopropyl by isobutyl substituents relieves the nitrogen of some of the crowding caused by the proximity of the CH(CH,), groups. Our results are limited to amides with primary and secondary alkyl substituents only. N,N-Di-tert-butylformamide is the only di-tert-substituted amide that has been synthesized. As explained above, this amide showed no chemical shift difference between cis- and trans-tert-butyl groups in the gas phase. Berg and B l ~ mhave ' ~ determined the liquid barrier for this amide in [*H8]tolueneto be 13.7 kcal mol-', a dramatic decrease over that of dimethylformamide (AG*liqE 2 1 kcal mol-'). The liquid spectra run for this study used 1 mol % solutions in CCI,. Carbon tetrachloride was chosen as solvent because it is nonpolar and incapable of hydrogen bonding. The low concentration of amide should minimize the amide-amide associations that occur in neat amides and concentrated solutions. In this way, we have attempted to minimize all liquid intermolecular effects, except solvent-packing forces. Previous studies3" of medium effects on amide rotational barriers used liquid barriers from existing studies, which were often determined in solvents that may exhibit numerous intermolecular effects. These studies readily confirmed that interactions in liquids raised the rotational barrier in amides but were inconclusive as to the quantitative effect of substituent size on the change in the barrier. Barriers in amides vary considerably with solvent; for example, N,N-dimethylacetamide barriers range from 18.2 (neat) to 19.3 kcal mol-' (H20) and N,N-dimethylbenzamide barriers from 14.0 (benzene/CSz 15%:85%) to 18.1 kcal mol-' (H20).2 Solvents that can hydrogen bond tend to raise the barrier. Other effects, although obviously present, are not well defined, as there is a shortage of reliable data. The contribution to the Gibbs activation energy by packing forces can be estimated by considering the steric contribution to the activation volume.8 If an amide molecule is to undergo a conformational change by rotation about the C-H bond, a region large enough to accommodate a 180' movement by each alkyl groups must be cleared of crowding molecules. This region can be assumed to occupy one-half the volume of a solid of revolution, centered on the C-N axis. The volumes for the two substituents are added together to obtain the total cleared volume necessary (14)
Berg, U.: Blum, 2 . J . Chem. Res., Symp. 1983. 206-207
Symmetrically Substituted N,N-Dialkyltrifluoroacetamides for rotation. The alkyl groups consist of 1-4 spheres, possibly overlapping, each with the diameter of a methyl group, 3.8 A.15 In the case of the isopropyl and isobutyl substituent, a sphere with a 2.2-A diameter was used to represent the methine hydrogen. The region occupied by the stationary overlapping spheres represents the ground-state volume and is subtracted from the area occupied by the solid of revolution, which represents the transition-state volume. Since the preferred conformations of the alkyl chains are not generally known, bond lengths, interatomic distances, and bond angles for the trifluoroacetamides were obtained from geometry-optimized molecular orbital calculations using the computer program A M P A C . ~ ~The calculated volumes occupied by the overlapping spheres are 53, 85, 112, and 126 A3 for DMTFA, DETFA, DIPTFA, and DIBTFA, respectively. The volumes occupied by the solids of revolution generated by rotating the overlapping spheres’ cross sections viewed from a point perpendicular to the xy plane above the x axis are about 78, 138, 131, and 144 A3 for the four trifluoroacetamides. The corresponding calculated activation volumes based solely on geometrical factors are I5 cm3 mol-’ for DMTFA, 20 cm3 mol-l for DETFA, 12 cm3 mol-’ for DIPTFA, and 1 1 cm3 mo1-I for DIBTFA. If it is assumed that the CF3 group rotates, AV would be ca. 18 cm3 mol-’ for all four amides. A logical assumption would be that the amide rotation occurs so as to minimize the activation volume and thus minimize AG*; therefore, the steric contribution to AV for DETFA may be as low a 18 cm3 mol-’. The contribution of packing forces to the liquid AG*’s is calculated from eq 1 by using the calculated activated volume and solvent internal pressures of 3037 atm for CC14.9The calculated AV’s for several amides are listed in Table V along with the associated value of AAG* from eq I . The calculated and experimental values of AAG* for the trifluoroacetamides match well, the largest deviation being exhibited by the dimethyl compound. The gas-phase value for the dimethyl compound is from a previous study in our group,6 and the liquid value from a 100-MHz study by Reeves et al. (1 1.25 mol 5% in CCI4).l7 The formamides do not show as good agreement, in(15) Verlet. L.; Weis, J.-J. Phys. Reu. A 1972, 5, 936-952. ( I 6) Program No. 506, Quantum Chemistry Program Exchange, Indiana University, Bloomington, IN 47405. The AMI Hamiltonian was used. (17) Reeves, L. W.; Shaddick, R. C.; Shaw, K . N. Can. J . Chem. 1971, 49, 3683-3691. (18) Drakenberg, T.; Dahlquist, K.; ForsBn. S. J . Phys. Chem. 1972, 76, 21 78-2183. (19) Hammaker, R. M.; Gugler, B. A . J. Mol. Spectrosc. 1965, 17, 356-364. ( 2 0 ) Sidall, T. H.; Stewart, W. E.; Knight, F. D. J. Phys. Chem. 1970, 74, 836-8 39. (21) Neuman, R. C., Jr.; Jonas, V . J. J . Am. Chem. SOC.1968, 90, 1970-1 975.
The Journal of Physical Chemistry, Vol. 94, No. 17, 1990 6683 dicating that dielectric effects may be important in polar solvents. The chemical shifts differences of the nitrogen substituent protons for the two conformers in the gaseous trifluoroacetamides differ from those in the liquid, but this difference is not as dramatic as that previously seen for the formamides.5 While formamides exhibited complete reversals in the size of the limiting chemical shift differences for the phase change, the trifluoroacetamides show only relative size differences. DMTFA, DETFA, and DIBTFA all have smaller A d s than their liquid counterparts while for DIPTFA, A a is larger. This is consistent with similar conformations for both phases. If conformational differences between phases were substantial, intramolecular effects on shielding might be expected to make more preferential differences in ACT,increasing or decreasing the value for one set of protons while not affecting or oppositely affecting the others. This is the case for the formamides but not the trifluoroacetamides. The higher limiting chemical shift differences in liquid- versus gas-phase trifluoroacetamides are more likely attributable to accentuations in shielding effects by the solvent or other amide molecules. Last, comparison of our gas-phase trifluoroacetamide results with the two gas-phase acetamides (dimethyl and diisopropyl) for which data are available (see Table IV) shows that the acetamides have lower activation energies than the corresponding trifluoroacetamides. Trends in amide barrier heights have been explained on the basis of the steric effects described above and/or substituent electronegativity. Higher substituent electronegativity at the carbonyl carbon increases the barrier by destabilization of the transition state in which the carbonyl carbon carries a partial positive change. When the barrier heights in acetamides and trifluoroacetamides are compared, the two effects compete. The CF3 group is somewhat larger than the CH3 group; the diameter estimated by using AMPAC results is 4.4 A for CF, versus 3.8 A for CH3.IS The larger size favors smaller barrier heights. The CF, group, however, is also more electronegative than the CH3 group, and this effect favors higher barrier heights. Gas-phase results indicate that electronic effects predominant, yielding higher barriers for trifluoroacetamides. Liquid-phase results are not conclusive. The activation energies for trifluoroacetamides can be larger than, equal to, or smaller than their acetamide counterparts. The magnitudes of the differences, however, are considerably smaller than in the gas phase, indicating that steric effects may be somewhat more important in liquid than in gaseous amides. Because of the inconsistency of the solvents used in the acetamide studies, further speculation is not possible.
Acknowledgment. We are pleased to acknowledge the National Science Foundation (CHE 85-03074 and C H E 83-50 1698 (PYI)), the National Institute of Health (GM 29984-04), and the Alfred P. SIoan Foundation for support of this research.
