25
J. Am. Chem. SOC.1982,104, 25-28
The 6-X-Benzonorbornyl System: A New Motional Dynamics Probe George C. Levy,*l" D. J. Craik,lbB. Norden, M. T. Phan Viet,lc and A. Dekmezian Contribution from the Department of Chemistry, Florida State University, Tallahassee, Florida 32306. Received May 7, 1981
Abstract: I3C NMR spin-lattice relaxation data have been used to probe solution molecular dynamics for a series of 6-X-benzonorbornene derivatives (X = NH2, CH3, NH3+). The benzonorbornyl system was chosen specifically because it
possesses structural features that make it a powerful probe molecule: rigidity, many nonequivalent C-H vectors, and overall low symmetry, but high local "phenyl" symmetry at the X group. Preliminary data obtained by using this probe are given, showing its application to the analysis of solvent-restricted rotation of NH3+in several solvent/anion systems. Overall molecular motion was also studied. The NMR relaxation data were analyzed by using a SIMPLEX optimizing interactive computer program based on the Woessner model for anisotropic motional diffusion. For the methyl and amine derivatives two factors were found to be important in determining overall motional anisotropy: (a) the inertial properties of the molecule and (b) the relative disturbance of neighboring solvent molecules arising from molecular rotation. Protonation of the amine resulted in decreased motion of the probe molecule as a whole as well as a considerable increase in the rate of internal spinning of the NH3+group compared with NH2 rotation/inversion, as determined from ISN TIDDmeasurements.
I3C spin-lattice relaxation times have been extensively used to study molecular A number of the studies to date have been concerned with motion in substituted benzenes (1),23335 where 2
Y
,,Lx
ax 1
it has been shown that the preferred in-plane rotation occurs about the molecular axis coincident with the phenyl ring-substituent bond. This effect was found to be magnified when the substituent was increased in size or when it was as~ociated.~ The usual approach applied in these studies was to determine the ratio of the T I value of either the ortho or meta carbons to that of the para carbon. A ratio of Tl(o,,,)/Tl(p) significantly greater than unity was assumed to indicate preferred motion about the in-plane Cz axis (x). Subsequently, Bauer et a1.I0 and Vold" showed that this simple approach was only valid when the substituent was large; otherwise, preferred rotation around the ( z ) axis perpendicular to the plane of the ring could lead to incorrect conclusions. The major difficulty associated with motional studies in substituted benzenes is that all of the ring C-H vectors are coplanar and thus I3C spin-lattice relaxation data can differentiate only two of the three rotational diffusion coefficients. In spite of this, (1)(a) Camille and Henry Dreyfus Teacher Scholar. (b) CSIRO Postdoctoral Student. (c) NSERC Postdoctoral Fellow. (2)Wright, D. A.; Axelson, D. E.; Levy, G. C. In "Topics in Carbon-13 NMR Spectroscopy", Levy, G. C., Ed.; Wiley-Interscience, New York, 1979; Volume 3, Chapter 2 and references cited therein. (3) Levy, G. C.; Cargioli, J. D.; Anet, F. A. L. J . Am. Chem. SOC.1973, 95, 1527. (4) (a) Grant, D. M.; Pugmire, R. J.; Black, E. P.; Christensen, K. A. J . Am. Chem. Soc. 1973,95, 8465. (b) Berger, S.;Kreissl, F. R.; Grant, D. M.; Roberts, J. D. Ibid. 1975,97, 1805. (5)Levy, G. C.; Godwin, A. D.; Hewitt, J. M.; Sutcliffe, C. J . Mugn. Reson. 1978., 29., 553. (6) Bleich, H. E.; Glasel, J. A.; Latina, M.; Visintainer, J. Biopolymers 1979.18.2849. ( 7 ) Beierbeck, H.; Martino, R.; Saunders, J. K. Can. J. Chem. 1980,58, 102. (8)Axelson, D. E.;Holloway, C. E. Can.J . Chem. 1980,58,1979. (9)Rtner, T. P.; Whidby, J. F.; Edwards, W. B. J. Am. Chem. SOC.1980, 102. ~.5149. (IO) Bauer, D. R.; Alms,E. R.; Brauman, J. I.; Pecora, R. J. Chem. Phys. 1974,61, 2255. ( 1 1) (a) Vold, R. R.;Vold, R. L. J. Chem. Phys. 1976,64,320. (b) Canet, D.; Vold, R. L.; Vold, R. R. Ibid. 1976,64,900.
these systems do have a number of important features (such as symmetry, rigidity, essentially equal C-H bond lengths, and off-axis C-H vectors which are close to the magic angle of 54.7') which combine to make substituted benzenes a very useful motional probe. However, a much superior system would be one which possessed the above features but did not have the disadvantages of planar systems. In this preliminary paper we propose the 6-X-benzonorbornyl system (2)as a new molecular probe for motional dynamic studies.
x
mi -
J
40
.
4
3
L
This system combines the advantages of the phenyl ring system with the rigid three-dimensionality of the norbornyl system: the overall symmetry of the molecule is low, giving 11 nonequivalent one bond C-H vectors. However, there is high local ("phenyl") symmetry at the X group which permits the investigation of changes in internal motional dynamics of this group. The effects of overall anisotropic tumbling of the molecule as a function of solvent (and counterion for charged substituents) can also be studied. The system is also ideally sized, i.e. not too large, so that it is possible to induce anisotropic motion when X is a group affected by intermolecular interactions or electrostatic effects. All of the above features are critical for the evaluation of anisotropic molecular reorientation and the use of this phenomenon to probe solution effects such as ion pairing and hydrogen bonding. In this paper, as well as presenting the 6-X-benzonorbornyl system as a motional dynamics probe, we also show a first application to the study of C H 3 and NH3+ group rotation. First, however, a brief description of some relevant theoretical background is given below. In general, when molecular motion is not isotropic or is outside the range of extreme narrowing or when the decay of the autocorrelation function is nonexponential, the equations relating spin-lattice relaxation times and terms related to molecular motion are c o m p l e ~ . ~ For ~ - ~simple ~ anisotropic or internal motional (12)Levy,G. C.;Lyerla, J. In "Topics in Carbon-13 NMR Spectroscopy"; Levy, G. C., Ed.; Wiley-Interscience, New York, 1974;Volume 1, Chapter 1. (13) London, R. E. 1n"Magnetic Resonance in Biology"; Cohen, J. S., Ed.; Wiley: New York, 1980. (14)Doddrell, D.; Glushko, V.; Allerhand, A. J . Chem. Phys. 1972,56, 3683.
0002-7863/82/1504-0025$01.25/00 1982 American Chemical Society
26 J. Am. Chem. Soc., Vol. 104, No. 1. 1982 dynamics the Woessnerl5formulation has found much application. For t h e case of a rigid molecule tumbling anisotropically in solution, t h e TI value for a given carbon can b e expressed as a function of three diffusion constants and three direction cosines
Here R , , R2, and R3 are the diffusion constants describing rotational motion a b o u t three mutually perpendicular axes. As an initial approximation it is normally assumed that the diffusion axis system is coincident with t h e inertial axis system (Le., t h e axis system in which t h e inertial tensor is d i a g ~ n a l i z e d ) . ~The *~ direction cosines I , m,and n represent t h e angles subtended by each C-H vector with respect to t h e three principal axes. These terms impart a geometrical dependence t o t h e T I values. Further details relating t o t h e exact functional f o r m of eq 1 are given in t h e Appendix. Recently it has been pointed out t h a t this type of analysis must be carried out with a careful regard for t h e appropriate limitations of t h e method.I6 If this is done, then i t is possible to semiquantitatively determine motional anisotropy and t o interpret this motion in t e r m s of t h e inertial or interacting properties of t h e system under investigation. In this type of study it is particularly important t h a t T I values are measured carefully a n d are determined t o t h e highest possible accuracy. I t is also imperative t h a t t h e iteration procedure used is suited t o the determination of an optimum point in a relatively shallow response surface. W e have found our SIMPLEX approach most applicable in this regard. I t should also b e noted t h a t the application of t h e Woessner equation presumes t h e presence of only isolated I3C-H dipolar autocorrelation terms. I t is possible t h a t cross-correlation effects may m a k e some contribution t o the relaxation of t h e three methylene groups in 2. However, for t h e proton-decoupled 13C d a t a discussed here such effects a r e of second order a n d a r e expected t o contribute errors of less t h a n 5%. Several groups1IJ7 have examined in detail t h e use of multiple relaxation interactions for the determination of diffusion tensors. Experimental Section The 6-X-benzonorbornene derivatives, with X = CHI and N H 2 (or NH3*) were synthesized by using adapted procedures from the literat ~ r e . ' ~ - ~For I the methyl derivative, 0.1 mol (15.1 g) of 2-amino-5methylbenzoic acid in 80 mL of T H F was added dropwise over 5 h to a refluxing solution of 0.2 mol (13.2 g) of cyclopentadiene and 0.12 mol (12.3 g) of isoamyl nitrite in 300 mL of dichloromethane. The mixture was refluxed overnight, the solvent evaporated, and the residue extracted with 400 mL of heptane, passed through a short column of alumina, concentrated, and distilled. A 7.2-g sample of 6-methylbenzonorbomadiene (1 14 OC, 25mmHg) was obtained. 6-Methylbenzonorbornene was obtained quantitatively by hydrogenation in ethyl acetate with 10% Pd/C. For an increase in the sensitivity of the I5N N M R experiment, the amine and its salts were isotopically enriched in ISN as follows: Benzonorbornadiene was reduced with H2/Pd-C in ethyl acetate at 2-3 atmospheric p r e s s ~ r e . 'The ~ resultant benzonorbomene was nitrated with a HNO3/HzSO4/H20 mixture (containing 15% ISN-labeled H N 0 3 ) in nitromethane at 0 OCS2OThe product was essentially the 6-NO2 isomer containing few percent of the 5-NO2 isomer. Separation was achieved by silica gel liquid chromatography. The 6-NO2-benzonorbornene was reduced to the amine by using Zn dust in ethanol and CaC12.z1 (15) Woessner, D. E. J . Chem. Phys. 1962, 37, 647. (16) Stilbs, P.; Moseley, M. E. J . Magn. Reson. 1979, 33, 209. (17) (a) Werbelow, L. G.;Grant, D. M. J . Chem. Phys. 1975,63,544. (b) Ado. Magn. Reson. 1977, 9, 189. (18) Inamoto, N.; Masuda, S.;Tori, K.; Aona, K.; Tanida, H. Can. J . Chem. 1967. 45. 1185. (19) Cu&he,'C. D.; Peter, H. H. 'Organic Synthesis"; Wiley: New York, 1963; Coll. Vol. IV, p 887. (20) Tanida, H.; Muneyuki, R. J . Am. Chem. SOC.1965,87, 4794. (21) Kuhn, W. E. "Organic Synthesis"; Wiley: New York, 1943; Coll. Vol. 11, p 447. (22) (a) Terabe, S.; Konaka, R. J . A m . Chem. SOC.1971, 93,6323. (b) Tori, K.; Yoshimura, U.; Muneyuki, R. Ibid. 1971, 93, 6324. (23) Burn, P. K.; Crooks, P. A.; Meth-Cohn, 0. Org. Magn. Reson. 1978, 11, 370.
Levy et al. Table I. Chemical Shifts of Benzonorbornene and Some 6-Substituted Derivatives"
X
1
2
H NO, NHZb NH, CH,
43.8 43.8 43.0 43.4 43.9
27.1 26.4 27.8 26.4 27SC
6
7
X H
NO,
E:b
CH,
125.5 146.6 144.3 126.1 134.9
120.8 111.7 119.7 126.0
3 26.4 27.3 26.4 27.4c 8 122.0 120.9 121.7 120.3
4
4a
5
43.8 44.0 43.8 43.5
148.1 149.6 149.7 151.0c 148.5
120.4 115.9 108.8 115.0 121.6
8a
9
CH,
155.9 138.7 150.2c 145.3
49.4 49.4 49.1 49.4 49.5
21.64
a In parts per million from Me,Si, 0.1 M solutions in C,D,CI,.
Trifluoroacetate salt.
Assignment may be reversed.
13C and 15N spectra were obtained on two superconducting solenoidbased spectrometers, at 37.7 and 27.4 MHz, respectively. The 'IC resonances of the benzonorbornene derivatives were assigned by using I3C additivity rules and comparisons with related compounds, shift reagents, paramagnetic relaxation (PAR) reagents, and decoupling techniques. 13C and 15N TI values were determined by using the FIRFTz4technique with A total of delay times of 3-5 s between the -(180-~-90)-sequences. l e 1 5 T values ranging from -0.01 s to 5T] s were used to obtain a given T I data set. The T I values given in Table I1 were obtained by using a three parameter exponential fit24and are estimated to be accurate to f 5 % . Careful NOE measurements (using the gated decoupling technique with a delay of IOT, between pulses) showed full enhancements for the protonated ring and methylene carbons, confirming the dominance of dipolar relaxation at these sites. A full NOE was not obtained for the methyl group in 6-methylbenzonorbornene, presumably because of a contribution from the spin-rotation relaxation mechanism. Within experimental error the maximum expected 15NNOE of -4.93 was obtained for the amine; however, smaller enhancements were noted in the protonated derivatives. Again, this most likely reflects spin-rotation contributions, as the NH, group undergoes faster internal motion than does NHZ. The calculations of the diffusion constants was carried out by using a FORTRAN 5 (Data General) program developed in our laboratories for an Eclipse S/130 minicomputer. For input, the program requires molecular coordinates in an arbitrary reference frame, the experimentally determined dipole-dipole TI values (TIDD)for three or more carbon atoms in the molecule, and initial guesses for the diffusion constants. The heavy-atom coordinates were obtained from a rudimentary molecular mechanics calculation. The hydrogen atom positions were calculated by assuming standard values for the carbon-hydrogen bond lengthsZS(1.09 8,for the aliphatic protons and 1.08 8, for the aromatic protons). Small deviations from these values are not expected to change the calculated diffusion constants, within the error limits specified in Table 111. IsN-lH bond lengths were set at 1.01 The program iteratively determines a set of diffusion constants which minimizes the sum of the squares of the deviations of the calculated and observed T Ivalues. Both nonlinear least squares and SIMPLEX techniques were used for iteration, with the latter method being found more satisfactory.
-
Results and Discussion I3C chemical shift d a t a for some of t h e substituted derivatives of (2) are given in T a b l e I. I3C a n d ISNTIDDd a t a a r e given in T a b l e 11. I t is apparent from t h e 13C dipolar T I d a t a for t h e methyl derivative that some degree of anisotropy is present in t h e motion. This can be seen, for example, in t h e nonequivalence of t h e T , values for t h e ring carbon positions 5 , 7, a n d 8; t h e TI of carbon 7 is significantly shorter t h a n those for carbons 5 a n d 8. A qualitative examination of t h e dipolar TId a t a for the amine a n d derivatives reveals a large decrease in overall motion upon protonation with trifluorosulfonic or trifluoroacetic acid. T h i s is indicative of strong solvation or ion pairing. Interestingly, t h e d a t a also indicate that protonation by acetic acid does not restrict t h e overall motion nearly a s much. I n a recent I5N a n d I3C relaxation studyS of aniline and aminobenzoic acid anions, neutral (24) Levy, G. C.; Lichter, R. L.; Nelson, G. L. "Carbon-13 Nuclear Magnetic Resonance"; Wiley-Interscience: New York, 1980; Chapter 8. (25) Pople, J. A,; Gordon, M. J . Am. Chem. SOC.1967, 87, 4354.
J . Am. Chem. Soc., Vol. 104, No. I , 1982 27
The 6-X- Benzonorbornyl System
Table 11. 37.71-MHz I3C T I D D Data for 0.5 M Derivatives and Salt? of the 6-X-Benzonorbornyl System in CDCl,CDCl, at 21 " C __
X
counterion
C-1
__
C-2
_ _ ~ _ _
C-3
__
I_-_-I__-___._____-_.___. -
C-4
C-5
C-7
C-8
CH,
C-9
~
NH,
b
1.41 0.57 0.59 1.55 1.71 1.35 1.58 0.58 6.3 (-4.82)' NH, 4.3 (-4.54) NH,' CH,COO1.15 0.48 0.46 1.24 1.42 1.16 1.25 0.48 NH,t CF,COO0.40 0.13 0.13 0.35 0.43 0.37 0.37 0.13 1.1 (-3.88) 0.40 0.16 0.16 0.35 0.44 0.37 0.38 0.15 2.3 (--.3.31) NH,+ CF,SO; 2.10 0.87 0.87 2.23 2.42 1.89 2.22 0.80 8.0 (1, 19)' CH, __ _ _ - ~ . I NOEF 'IN TIDDsand NOEFs at 27.36 MHz. The salts were prepared by adding a 10% excess of the appropriate acid to the amine. values are given in parentheses for CH,,NH, and NH;. The theoretical maximum NOEF values were observed for all other protonatrd carbons.
species, and cations, the activation energy for overall molecular reorientation and for the composite internal overall motion of the -NH2 and -NH3+ groups was e ~ t i m a t e d . ~It was found that although the -NH3+ groups spins faster than -NH2, its rotation was quite restricted compared to -CH3 rotation in analogous systems. However, diprotonation of m-aminobenzoic acid with the nonnucleophilic superacid CF3S06Hgave Ti data indicative of extremely rapid -NH3+ group internal rotation relative to overall reorientation. It is apparent from the current study that the NH3+group of 2 undergoes rapid spinning in the presence of the CF3S03counterion. This can be seen, for example, by noting that the carbon T1data sets for the trifluoroacetate and trifluorosulfonate salts are very similar, but the nitrogen dipolar Ti values are more than a factor of 2 different. The larger TIDD value for the NH3+ group in the trifluorosulfonate salt indicates faster NH3+rotational motion. The I5N NOE values in Table I1 confirm these general conclusions. The full enhancement (theoretical -4.93, observed -4.8) noted for the amine N H 2 group decreases upon protonation in the order CH3COO- > C F 3 C O 0 > CF3SO
