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Natural abundance 15N and 13C spectroscopy. Aminobenzoic acids, substituted anilines, and related compounds
.?OURNAL
OF MAGNETIC
RESONANCE
29,553-562
(1978)
atural Abundance 15N and 13C Spectroscopy. Aminobenzoic Acids, Substituted Anilines, and Related Compounds GEORGE C. LEVY,* ALLEN D. GODWIN, JAMES M. HEWITT, AND CAROL SUTCLIFFE Department
of Chemistry,
The Florida
State
University,
Tallahassee,
Florida
32306
Received July 19, 1977 Combined use of carbon-13 and nitrogen-is NMR spectral data can give unique insight into the molecular dynamics of nitrogen-containing organic compounds and ions. r3C and 15N spin-lattice relaxation data and chemical shifts are reported for aniline and also for o-, m-, and p-aminobenzoic acids in solution as the cations, anions, and neutral compounds. r5N and t3C dipolar. T, values obtained as a function of temperature for aniline and anilinium ion allowed estimation of the activation energy for overall molecular reorientation (IV T,‘s) and for the composite internal-overall motion of the amine functions (r5N T,‘s). The calculated values using both nuclei were the same: 3 kcal mole-t for aniline and 4.8 kcal mole-’ for anilinium ion. “C spin-lattice relaxation times (Tr’s) for the neutral and ionized aminobenzoic acids probe inter- and intramolecular association through hydrogen bonding and ion pairing. t3C and 15N relaxation and shielding data give evidence for possible intramolecular association between the amine and carboxyl functions in ortho-aminobenzoic acid and its mono-ions. 15N T, and nuclear Overhauser enhancement (NOE) data indicate that aniline or substituted aniline NH, or NH,+ groups undergo rapid but not free internal rotation (and/or inversion in the case of NH, groups), at rates at least comparable with the rate of overall reorientation for these systems (7, Z lo-r0 set). o- and m-Aminobenzoic acids are effectively diprotonated in CF,SO,H solution. r5N T,‘s and NOE’s for these two species indicate that the NH,+ groups spin essentially freely in this highly acidic, nonnucleophilic medium.
h the advent of modern NMR instrumentation, measurements of natural ab ante 13C spin-lattice relaxation times @i’s) have become routine in many laboratories (I, 2). These data have, in turn, been successfully used to characterize molecular motions in liquid systems (3). Investigations of i5N relaxation times, however, have been limited primarily to a few isotopically enriched compounds (4) because of the inherent difficulty of the 15N NMR experiment. The 15N nucleus has a spin of 1 and gives rise to sharp resonance lines. But the small, negative i5N magnetogyric ratio and the low natural abundance (0.36%) combine to greatly decrease NMR sensitivity for this nucleus. This situation is coupled with oftenle negative nuclear Overhauser (NOE) effects (5); thus the practicality of the experiment diminishes even further. However, with the use of high magnetic arge sample tubes, and quadrature detection, greater 15N sensitivity can be thieved (6, 7) and at concentrations 71 A4 natural abundance 15N Ti measurements are now feasible. * Alfred P. Sloan Fellow, 1975-1977; Camille and Henry Dreyfus Teacher-Schoiar, 1976-1981. 0022%2364/i8/0293-0553%02.00/O 553
Copyright 0 1978 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
LEVY
554
ET
AL.
Early experiments indicated that because of the rather long spin-lattice r~l~~at~o~ times associated with the i5N nucleus (4), the practicality of lSN Tl experiments would be very limited. It was subsequently shown that this prediction was premature, in part, for recent studies have reported 15N Tl's of the order of 1 set or less for many bearing nitrogens (7). In continuing our investigations of the relaxation behavior of organic molecules, we present here natural abundance 13C and 15N studies of three aminobenzoic acids, as nonionized and charged species. Using the ionizable aminobenzoic acids, molecular motion can be controlled, simulating behavior of much larger molecules. This can occur particularly through two effects: (1) ion-pair and ion-solvent association, and (2) carboxylic acid dimerization. Also reported here is the effect of temperature on the 13C and r5N Ti behavior of aniline and anilinium ion. A combination of r5N and 13C T, and NOE measurements on the individual species was used to evaluate whether the NH, or NH,+ groups undergo rapid internal rotation (in the latter case, by analogy to the sterically similar CH, group of toluene). EXPERIMENTAL
All samples were commercial materials, recrystallized or distilled prior to use. Samples were degassed by purging with N,. NMR spectra were obtained on a quadrature detection-modified Bruker HX-270 spectrometer, in 13- and 15-mm sample tubes. Reported temperatures were measured directly by sample substitution and are reproducible to better than 2OC. viscosities were measured using Cannon Manning microviscosimeters. 13C and l of the anilines and aminobenzoic acid derivatives were obtained using the I FIRFT technique (8) and are considered to be accurate by + 10% or better. For a few of the FIRFT lJN T, measurements infinity r values were not obtained. In these cases a
’
1.8 2.5
3.2
4.0
5.0
8.0
FIG. 1. Inversion recovery FT NMR spectra for 4.0 M sodium m-aminobenzoate pulse sequence repetition rate was 12 set: 120 scans were accumulated.
30
in D,B
(4OOC).
The
ANILINES
AND AMINOBENZOIC
555
ACIDS
three-parameter exponential fit (9) was used to calculate T,, +10-B%. (The resulting time saving has designated this experiment as SUPER FIRFT (IQ).) For the NOE data, gated decoupling using long delay times at least equal to 10 T, and, more commonly, 15 T, was employed (11). A typical example of a natural abundance 15N I experiment for 4.0 M m-aminobenzoate in water is shown in Fig. 1. For each r value, 220 scans were collected. The total experimental time in this case was 3.2 hr. RESULTS AND DISCUSSION
Anilines and Anilinium Ions
Temperature-dependent 13C and 15N relaxation data for aniline and the anilinium ion are presented in Table 1. 15N spectra for both of these compounds show essentially full NOE’s, indicating that dipole-dipole interactions with protons dominate 15N relaxation behavior in these cases. With an increase in temperature there is a corresponding increase in observed dipolar Ti (eD) values, giving calculated apparent rotational motion activation energies of ca. 3 kcal mole-’ for the NH, group of aniline and ca. 4.8 kcal mole-’ for the NH,+ group of anilinium trifluoroacetate (in CDCl,). TABLE 1 ‘TEMPERATURE-DEPENDENT13CAND 15N RELAXATION DATA: ANILINE AND ANILINIUM ION 13C Relaxation data lSN Relaxation data Temp”
T,
NOEF (-q)
13CTl (set) TYDb
Ternpa
c-2,
c-3,
C-4
Anilinec (95% enriched) -4 6 16 24 35 50
21.3 25.5 30.0 31.5 34.1 52.5
4.9 4.5 4.6 4.6 4.5
22 33 34 37 58
-46 +21 +43
2.3 13.2 17.5
2.1 10.8 15.4
Anilinium ion d(95% enriched) -4
0.78
6 16 24 35 50
1.1 1.5 1.6 2.2 3.1
4.0 4.4 4.8 5.1
0.97 1.1
-7
0.70
+8
1.0
1.6 1.6
-i-31
2.6
4.9
3.1
0.2 1 0.33 0.63
a Temperature in “C + 2”; measured directly on the samples. b Calculated from Tf’” = T, (obsd) . (q max/q obs). e LOMin CDCl,. d 1.0 M in CDCl, with an equivalent amount of trifuloroacetic acid plus three drops of glacial acetic acid present. e Assumed fully dipolar.
556
LEVY ET AL.
These calculated activation energies may actually be composite parameters for the processes of overall molecular reorientation and internal rotation. In fact, the observed values appear to arise largely from the overall reorientation process. This follows from the 13C T1’s for the ring carbons of aniline and the anilinium ion (Table 1). First of all, the approximate reorientational activation energies obtained from the 13C data are consistent with the more-accurate lSN-derived values. (More temperatures were used for the 15N data.) Furthermore, the relative magnitudes of 13C and lsN dipolar T1’s indicate that the NH, and NH,+ groups may be spinning at a rate comparable with the overall reorientational rate (7, 5 lo-lo set). Thus, only a small ((3 kcal mole-‘) activation energy is expected for the internal rotational motion. In the absence of internal motion, and assuming isotropic reorientation (approximated for the free amine but not actually valid for the anilinium ion’), the dipolar 15N T,‘s would be 2 and 1.3 times longer than the ring 13C Tl’s, i.e., for the NH, and NH?+ groups, respectively. Observed or interpolated 15N vs 13C Tl’s obtained on both aniline and the cation in CDCl,, in ratios of 3 : 1 to 4: 1, give evidence of some internal rotation.2 Taking into account the principal diffusion axis of the cation, and the tetrahedral geometry of the NH,+ group, it appears qualitatively that internal motion may be somewhat more restricted in anilinium trifluoroacetate (in CDCl,) than in aniline itself. This may be contrasted with behavior reported below for the dications of ovtho and mela aminobenzoic acids in strongly acidic and nonnucleophilic triflic acid solution. 15N T,‘s were also obtained on 4 A4 DMSO-d, solutions of meta- and parasubstituted anilines. In all cases dipolar relaxation was essentially complete, observed T, values being 3 to 12 sec. The more polar NO, substituent resulted in the shortest NH, T1 [3.3 set (para) and 3.9 set (meta)]. Meta-CH, andpara-Br substituents resulted in T,‘s of 6.9 and 4.9 set, respectively (versus 12.1 set for aniline itself at this concentration in DMSO-d,). Some qualitative observations were also made on the effects of paramagneti~ materials in these aniline samples. With incremental addition of Ni(acac),, incremental reduction in the T, of the amine nitrogen was observed. The NOE -was reduced effectively to zero (Tl z 0.5 see) with the addition of on& I x low4 M Ni(acac),. These results f&her emphasize the importance of reporting NOE measurements along with 15N relaxation data. Aminobenzoic Acids and Ionized Derivatives 13C and 15N chemical shifts for the ortho, meta, and para aminobenzoic acids are
presented in Table 2. Protonation of the amino group with trifluoroacetic acid (TFA) results in an upfield nitrogen chemical shift of 9 to 12 ppm. Protonation leads to ‘i’- to IO-ppm deshielding for the carbons ortho and para to the amino group and ca. 2-ppm deshielding for carbons in the meta position. Formation of the anion, by reacting the aminobenzoic acids with an equivalent amount of sodium bicarbonate in water, generally produces 13C shifts to lower fields of ’ There are insufficient nonequivalent C-H vectors in aniline to perform accurate calcuiations of overall motional anisotropy. For the anilinium ion the principal diffusion axis lies along the ring substituent axis. * In the case of the NH, group, very rapid inversion at nitrogen may also give rise to effective “N4-I dipolar relaxation, and thus this alternative mode of internal motion cannot be ruled out.
ANILINES
AND AMINOBENZOIC
557
ACIDS
TABLE 2 13C AND 15NC~~~~~~~S~~~~~
OFAMINOBENZOICACIDS
PC Solution
c-2
2-Aminobenzoic acid Neutral” Cationb Anion’ 3-Aminobenzoic acid NeutraP Cationb AnionC
115.8 124.1 117.5
4-Aminobenzoic acid Neutrala Cationb AnionC
130.9 132.8 131.9
PNd
c-3
c-4
C-5
C-6
NH,, “NH,”
115.7 123.2 119f
134.4 136.2 132.3
117.0 124.6 1201
131.9 133.7 133.0
43.5 33.6 30.3
118.7 127.5 119.6
129.7 130.7 130.1
119.5 129.2 120.7
36.9 27.8 29.4
113.5 120.8 115.5
130.9 132.8 131.9
45.7 33.9 37.4
113.5 120.8 115.5
a 4 Min DMSO-d,, relative to TMS, referenced internally to DMSO (=40X@. b 4 M in DMSO-$ with 1 equiv of CF,CO,H, referenced internally to DMSO (=40.06). c Sodium salt, 4M in D,O, referenced internally to dioxane (167.4s). d Referenced externally to a saturated aqueous NH&l solution (= 0.06). e Ring carbon chemical shifts indicate that the amine function is not protonated in either the basic or neutral solutions; protonation is effected with the stronger acid, CF,CO,H [cf. Ref. (7)l. r Assignments interchangeable.
about 1 to 3 ppm in magnitude. One exception is observed: the C-4 carbon of 2aminobenzoate is shifted upfield by 2.1 ppm. The C-4 upfield shift may be a result of an intramolecular amine-carboxylate association (see below), where additional electron density might be expected for the ring carbonpara to the carboxylare anion. It should be noted that exact comparisons of the shieldings for the anions with those observed for the cations cannot be made, since some of these observed shift differences are due presumably to solvent effects. However, it can also be seen that the shift differences are not uniform for the three anions. For the 3-amino and 4-amino sodium benzoates, the nitrogen resonance is shifted upfield by 7.5 and 8.3 ppm, respectively, while the nitrogen of the 2-amino compound is shifted upfield by almost twice that amount (13.2 ppm). The latter effect might be attributed to intramolecular ‘“salvation” interaction between the amino hydrogens and the carboxylate anion, forming a sixmembered ring: H LN/H,.. iL3 0
cko
b
The above explanation is consistent with trends in the r5N and 13C relaxation data (see below).
558
ET AL.
LEVY
13C and 15N relaxation data for the 3substituted aminobenzoic acids are given in Table 3. Comparison of the T, data for these compounds indicates that the T,‘s for the anions are much longer than those observed for the cations and neutral species. Measured macroscopic viscosities for the anion solutions in D,Q are far lower than the viscosities for the neutral acids and cations in DMSO-& However, the re~atio~s~~~ between the lower anion solution viscosities and the longer observed T,‘s is not a simple one. An order-of-magnitude increase in macroscopic viscosity lengthens the r3C Tr’s by only a factor of 2 to 5. TABLE
3
r3C Relaxation
data
“N
Relaxation
data
T, (secjd
NOEF C-d
pm 1
T, (sec)d Viscosity Solution
(cp)
2-Aminobenzoic Neutral0 Cation* AnionC
acid
3-Aminobenzoic Neutral’ Cationb Anion’ 4-Aminobenzoic Neutrala Cation* Anion’
acid
n * c d with
c-2
11 -50 4.5
26 -50 2.9
0.44 0.25 1.05
24 33 2.3
0.34 0.27 0.65
c-3
c-4
0.42 0.21 1.6
0.26 0.22 1.1
0.37 0.23 1.6
0.32 0.25 1.3
0.57 0.39 3.67
4.3 3.8 4.8
0.65 0.5 1 3.71
0.27 0.17 0.66
0.46 0.26 0.89
0.45 0.17 0.90
0.68 0.43 3.90
3.8 3.8 4.1
0.88 0.56 4.69
0.33 0.29 0.68
0.34 0.27 0.65
0.54 0.30 3.54
3.1 3.7 4.1
0.86 0.40 4.26
all samples
were
C-5 or C-6
acid
4.0 M in DMSO-d,. 4.0 M ion DMSO-d, with an equivalent Sodium salt 4.0 M in D,O. All Tr’s were measured at 40 + 2OC nitrogen prior to use.
0.33 0.29 0.68
amount
of trifluoracetic
and at a field strength
acid. of 63.1
kG;
degassed
In the neutral and acidic solutions, these aromatic carboxylic acids form well-defined dimers as a result of their ability to create two strong intermolecular hydrogen bonds, forming a favorable ring (13): the cations, in addition, have restriction on their motion
imposed by ion-solvent and ion-pair interactions. Thus the 13C Tl’s are shorter by a factor of ca. 2 for the cation of 3-aminobenzoic acid (versus the nonionized acid). contrast, the decrease in i3C T,‘s for the 2- and 4-aminobenzoic acid cations is considerably smaller. In the case of the 2substituted cation presumably the relative
ANILINES
AND AMINOBENZOIC
ACIDS
5.59
mobility results from transient internal association between the NH,+ and the C groups:
(This internal association would compete with intermolecular association of the carboxyl group.) For the 4-substituted aminobenzoic acid the small decrease in 13CT,‘s for the cation relative to the neutral acid may result from internal phenyl rotation. In basic solution, the proton of the carboxylic acid moiety is removed and thus strong carboxylic acid dimerization cannot occur. As a result, the effective molecular size is decreased, mobility increases, and longer T,‘s are observed. The relatively long 13C Ti’s observed for the 2-aminobenzoic acid anion are consistent with intramolecular %olvation” of the carboxylate group, resulting in increased overall molecular reorientation. The solution macroscopic viscosity for the anions also indicates anomolous behavior for the 2-anion. The 2aminobenzoate solution viscosity is nearly twice as high as the viscosities of the 3- and 4-anions, and yet the 2-ion mobility is increased. The 15N T, for the 2-anion is short relative to the 13C TI’s, compared with the analogous values for the 3- and 4-anions. This is also consistent with the intramolecular “solvation” picture since it indicates less NH, internal motion. Comparison of the NH, and the NH,+ dipolar Tl’s with the ring carbon Tl’s for the aminobenzoic acid derivatives (vide supra) indicates that the amino functions-do not undergo unhindered internal spinning in the nonionized acids or in the cations. However, these groups do appear to undergo rapid internal motion, which in the anions is par$icularly fast. Faster NH, group internal rotation or inversion in the anions might be due to reduced conjugation between the NH, group and the electron-rich phenyl ring of the anion. In investigating the principal axes of rotation for these molecules, the 13C Tr data indicate that the nonionized amine group has little apparent effect on the overall rotation of the molecule [as noted previously (14)l. However, when the amine group is protonated, a substantial T, decrease is observed for carbons paru to the NH3+ group. The guru carbon T, probes the slower overall motion of monosubstituted benzenes [provided that the substituent is effectively a large group (15)l while the ortho and meta carbon T,‘s can give an indication of rapid overall or internal motion around the ringsubstituent symmetry axis. Qualitative predictions can be made regarding changes of axes of rotation for the present compounds:
0.37
(estimated principal axis of diffusion shown)
0.23
560
LEVY ETAL.
From these data it is evident that the NH, group plays very little part in the overall motion of these molecules. However, upon protonation and complexation with the solvent and CF,COOcounteranion, the amino group becomes important for molecular reorientation. The ration T, (ortho or meta)lT, (para) has been shown to be a measure of the preference for anisotropic reorientation in substituted benzenes.3 This ratio can be used as a further probe of motional change induced by molecular dimerization. For 2aminobenzoic acid the ratio of Ty-3!Tp4 is 1.6. For the corresponding anion, the ratio decreases to 1.4. For the 3-aminobenzoic acid and the sodkrm benzoate derivative, the ratios (Tc-s/Ty-4) are 1.7 and 1.3, respectively. The decreases in these two sets of ratios ;l are attributed to long-lived aminobenzoic acid dimem (13) which are present in the neutral solutions but are absent for the carboxylate anions. Wications of 2- and 3-Aminobenzoic Acids
In anilinium trifluoroacetate and the aminobenzoic acid monocations, the l5 13C TI data gave little evidence for rapid spinning of the NH,+ groups. The sterically similar CF, group of toluene, by contrast, spins very rapidly with essentially zeroenergy barrier for group rotation (16,12). Two explanations for the dissimilarity of the NH,+ group internal rotation might be: (1) restriction of rotation by strong solvent or counteranion interactions, or (2) restriction of rotational motion in the equilibrating nonionized aniline (or derivative). With protonated 2- or 3aminobenzoic acid in CF,SO,H (trifiic acid, a super-acid with H,, 5 14) solution it appears that the NH,+ groups do spin rapidly. The Tr‘spectral data for diprotonated 3-aminobenzoic acid are shown in Fig. 2. This experiment, at 1 M concentration and natural abundance, required 8 h using FI
15N,NATURAL ABUNDANCE, I MOLAR, 32°C +NH3 (CF3 SO,)2
c.0
Tl -2.2sec CO2 H; I
I
ii i
1.5
1.8 '2.0 2.5 3.0 3.5 4.0 8.8
FIG. 2. Fast inversion recovery FT NMR spectra for 1.0 M m-aminobenzoic The pulse sequence repetition rate was 2.8 set; 600 scans were accumulated. 3 Higher
Tf,m/q ratios
indicate
increased
( T values in set 1
anisotropy
(see Ref. 12).
acid in CF,SO,H
(32°C).
ANILINES
AND AMINOBENZOIC
ACIDS
561
the r values exceeding 3 set had been omitted, the total experimental time for the resulting 1 A4 lsN SUPER-FIRFT experiment would have been ca. 4 br). 0
CF,SO, 0
0 CO,H
0.19
CF,SO, 0
;;J;
0.19 0.19 13C and 15N T,‘s indicated (set) liN NOEF in ( ); [All data: 32”C, 1.0 M solutions in CF,SO,Hl
The 15N dipolar T1’s for the two dications are observed to be an order of magnitude than the ring carbon Tl’s. This indicates that the rate of NH,+ group internal rotation is very rapid relative to overall reorientation of the dications in this very acidic nonnucleophilic medium. This is perhaps surprising with the 2-dication, since strong ortho steric interactions might be expected to prevent “free” rotation. To confirm the results for the dications of the aminobenzoic acids, a solvent study was undertaken for the unsubstituted anilinium ion. Table 4 lists 13C and 15N relaxation data for an&urn trifluoroacetate in several solvents. In the relatively basic or nucleophilic solvents the ratio between the o&o or meta CH carbon TI’s and the 15NH3 T, is between 1 and 2, while in CF,CO,H the analogous ratio rises above 2. In the very nonnucleophilic triflic acid tPle nitrogen/carbon T, ratio is ca. 6. It is not a simple matter to separate motional contributions for these anilinium ions quantitatively, as a result of anisotropic overall reorientation and the lack of resolution longer
TABLE 4 13C
AND
15N
T,
DATA
FOR
ANILINIUM SOLVENTS
TRIFLUOROACETATE
IN
SEVERAL
“C T, (set)
Solvent and concentration H,O (l.OM) (0.1 M) CH,OH (LOM) CH,CN (0.1 M) CH,SOCH, (1.0 M) (0.1 M) CF,CO,H (1.0 M) (0.1 M) CF,SO,H (1.0 M) (0.1 M)
ortho
meta
para
10.2 10
10.4 11 8 11.3 3.4 2.5 b b b b
5.1 5.4 5.4 5.4 1.2 1.0 b b b b
1
11.1 3.2 2.0 2.0 5 2.0 3.2
15N T, (set)
16 19 1.4 8.4 3.0 4.0 I 12 12 17
63 kG and 40°C, T,‘s i IO-15%. All relaxation dipolar. b The meta andpara resonances coincide; no calculation of T, was possible,
“At
562
LEVY ET AL.
forqml
in the CF,CO,H and CF,SO,H solvents. Nevertheless, the large increase in the nitrogen/carbon T’, ratio in CF,SO,H is qualitative proof of greatly increased internal rotation of the +NH, group. ACKNOWLEDGMENTS We gratefully acknowledge support of this research by the National Science Foundation and the Donors of the Petroleum Research Fund, administered by the American Cheniical Society. We also thank Ely Lilly and Company for a grant-in-aid. Professor Clive E. Holloway and R. C. Allen provided helpful discussion. REFERENCES 1. A. OLNSON AND E. LIPPMAA, Chem. Phys. Lett. 11,241 (197 1). 2. K. F. KUHLMANN AND D. M. GRANT, J. Chem. Phys. 55,2998 (1971). 3. J. GRANDJEAN AND P. LASZLO, Mol. Phys. 30, 413 (1975); G. C. LEVY, T. STBIGEL, J. Amer. Chem. Sot. 98,495 (1976); U. EDLLJND, C. E. HOLLOWAY,
A. HOL~K, AND A. AND G. C. LEVY, J.
Amer. Chem. Sot. 98,5069 (1976). SCHWEITZER AND H. W. SPIESS, J. Magn. Resonance 16, 243 (1974); R. A. COOPER, LICHTER, AND J. D. ROBERTS, J. Amer. Chem. Sot. 95, 3724 (1973); D. D. GI~INI, ARMITAGE, H. PEARSON, D. M. GRANT, AND J. D. ROBERTS, J. Amer. Chem. Sot. 91,3416 E. LIPPMAA, T. SALUVERE, AND S. LAISAAR, Chem. Phys. Lett 11,120 (1971). 5. G. E. HAWKES, W. M. LITCHMAN, AND E. W. RANDALL, J. Magn. Resonance 19,255 (1975). 6. D. GUST, R. B. MOON, AND J. D. ROBERTS, Proc. Nat. Acad. Sci. USA 72,4696 (1975). 7. G. C. LEVY, C. E. HOLLOWAY, R. C. ROSANSKE, J. M. HEWITT, AND C. H. BRADLEY, Org. 4. D.
R. L. I. M.
(1975);
Maen.
Resonance 8,643 (1976). 8. ?. CANET, G. C. LEVY, AND I. R. PEAT, J. Magn. Resonance 18,199 (1975). 9. J. KOWALEWSKI, G. C. LEVY, L. F. JOHNSON, AND L. PALMER, J. Magn. Resonance 10. M. SASS AND D. ZIESSOW, J. Magn. Resonance 25,263 (1977); L. F. JOHNSON,
26,533 (1977). JR., at the NATO
Advanced Study Institute in Palermo, Italy, Sept. 1976. 11. R. FREEMAN, H. D. W. HILL, AND R. KAPTEIN, J. Magn. Resonance I, 327 (1972); S. J. @ELLA, D. J. NELSON, AND 0. JARDETZKY, J. Chem. Phys. 64, 2533 (1976); R. K. HARRIS AND R. H. NEWMAN, J. Magn. Resonance 24,449 (1976). 12. G. C. LEVY, J. D. CARGIOLI, AND F. A. L. ANET,J.Amer. Chem. Sot. 94,1527 (1973). 13. G. C. LEVY AND D. TERPSTRA, Org. Magn. Resonance 8,658 (1976), and references therein. 14. G. C. LEVY, J. Magn. Resonance 8, 122 (1972); references cited in (12). 15. D. R. BAUER, G. R. ALMS, J. I. BRAUMANN, AND R. PECORA, J. Chem. Phys. 61,2255 (1974). 16. C. F. SCHMIDT AND S. I. CHAN, J. Magn. Resonance 5,151 (1971).
OF MAGNETIC
RESONANCE
29,553-562
(1978)
atural Abundance 15N and 13C Spectroscopy. Aminobenzoic Acids, Substituted Anilines, and Related Compounds GEORGE C. LEVY,* ALLEN D. GODWIN, JAMES M. HEWITT, AND CAROL SUTCLIFFE Department
of Chemistry,
The Florida
State
University,
Tallahassee,
Florida
32306
Received July 19, 1977 Combined use of carbon-13 and nitrogen-is NMR spectral data can give unique insight into the molecular dynamics of nitrogen-containing organic compounds and ions. r3C and 15N spin-lattice relaxation data and chemical shifts are reported for aniline and also for o-, m-, and p-aminobenzoic acids in solution as the cations, anions, and neutral compounds. r5N and t3C dipolar. T, values obtained as a function of temperature for aniline and anilinium ion allowed estimation of the activation energy for overall molecular reorientation (IV T,‘s) and for the composite internal-overall motion of the amine functions (r5N T,‘s). The calculated values using both nuclei were the same: 3 kcal mole-t for aniline and 4.8 kcal mole-’ for anilinium ion. “C spin-lattice relaxation times (Tr’s) for the neutral and ionized aminobenzoic acids probe inter- and intramolecular association through hydrogen bonding and ion pairing. t3C and 15N relaxation and shielding data give evidence for possible intramolecular association between the amine and carboxyl functions in ortho-aminobenzoic acid and its mono-ions. 15N T, and nuclear Overhauser enhancement (NOE) data indicate that aniline or substituted aniline NH, or NH,+ groups undergo rapid but not free internal rotation (and/or inversion in the case of NH, groups), at rates at least comparable with the rate of overall reorientation for these systems (7, Z lo-r0 set). o- and m-Aminobenzoic acids are effectively diprotonated in CF,SO,H solution. r5N T,‘s and NOE’s for these two species indicate that the NH,+ groups spin essentially freely in this highly acidic, nonnucleophilic medium.
h the advent of modern NMR instrumentation, measurements of natural ab ante 13C spin-lattice relaxation times @i’s) have become routine in many laboratories (I, 2). These data have, in turn, been successfully used to characterize molecular motions in liquid systems (3). Investigations of i5N relaxation times, however, have been limited primarily to a few isotopically enriched compounds (4) because of the inherent difficulty of the 15N NMR experiment. The 15N nucleus has a spin of 1 and gives rise to sharp resonance lines. But the small, negative i5N magnetogyric ratio and the low natural abundance (0.36%) combine to greatly decrease NMR sensitivity for this nucleus. This situation is coupled with oftenle negative nuclear Overhauser (NOE) effects (5); thus the practicality of the experiment diminishes even further. However, with the use of high magnetic arge sample tubes, and quadrature detection, greater 15N sensitivity can be thieved (6, 7) and at concentrations 71 A4 natural abundance 15N Ti measurements are now feasible. * Alfred P. Sloan Fellow, 1975-1977; Camille and Henry Dreyfus Teacher-Schoiar, 1976-1981. 0022%2364/i8/0293-0553%02.00/O 553
Copyright 0 1978 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
LEVY
554
ET
AL.
Early experiments indicated that because of the rather long spin-lattice r~l~~at~o~ times associated with the i5N nucleus (4), the practicality of lSN Tl experiments would be very limited. It was subsequently shown that this prediction was premature, in part, for recent studies have reported 15N Tl's of the order of 1 set or less for many bearing nitrogens (7). In continuing our investigations of the relaxation behavior of organic molecules, we present here natural abundance 13C and 15N studies of three aminobenzoic acids, as nonionized and charged species. Using the ionizable aminobenzoic acids, molecular motion can be controlled, simulating behavior of much larger molecules. This can occur particularly through two effects: (1) ion-pair and ion-solvent association, and (2) carboxylic acid dimerization. Also reported here is the effect of temperature on the 13C and r5N Ti behavior of aniline and anilinium ion. A combination of r5N and 13C T, and NOE measurements on the individual species was used to evaluate whether the NH, or NH,+ groups undergo rapid internal rotation (in the latter case, by analogy to the sterically similar CH, group of toluene). EXPERIMENTAL
All samples were commercial materials, recrystallized or distilled prior to use. Samples were degassed by purging with N,. NMR spectra were obtained on a quadrature detection-modified Bruker HX-270 spectrometer, in 13- and 15-mm sample tubes. Reported temperatures were measured directly by sample substitution and are reproducible to better than 2OC. viscosities were measured using Cannon Manning microviscosimeters. 13C and l of the anilines and aminobenzoic acid derivatives were obtained using the I FIRFT technique (8) and are considered to be accurate by + 10% or better. For a few of the FIRFT lJN T, measurements infinity r values were not obtained. In these cases a
’
1.8 2.5
3.2
4.0
5.0
8.0
FIG. 1. Inversion recovery FT NMR spectra for 4.0 M sodium m-aminobenzoate pulse sequence repetition rate was 12 set: 120 scans were accumulated.
30
in D,B
(4OOC).
The
ANILINES
AND AMINOBENZOIC
555
ACIDS
three-parameter exponential fit (9) was used to calculate T,, +10-B%. (The resulting time saving has designated this experiment as SUPER FIRFT (IQ).) For the NOE data, gated decoupling using long delay times at least equal to 10 T, and, more commonly, 15 T, was employed (11). A typical example of a natural abundance 15N I experiment for 4.0 M m-aminobenzoate in water is shown in Fig. 1. For each r value, 220 scans were collected. The total experimental time in this case was 3.2 hr. RESULTS AND DISCUSSION
Anilines and Anilinium Ions
Temperature-dependent 13C and 15N relaxation data for aniline and the anilinium ion are presented in Table 1. 15N spectra for both of these compounds show essentially full NOE’s, indicating that dipole-dipole interactions with protons dominate 15N relaxation behavior in these cases. With an increase in temperature there is a corresponding increase in observed dipolar Ti (eD) values, giving calculated apparent rotational motion activation energies of ca. 3 kcal mole-’ for the NH, group of aniline and ca. 4.8 kcal mole-’ for the NH,+ group of anilinium trifluoroacetate (in CDCl,). TABLE 1 ‘TEMPERATURE-DEPENDENT13CAND 15N RELAXATION DATA: ANILINE AND ANILINIUM ION 13C Relaxation data lSN Relaxation data Temp”
T,
NOEF (-q)
13CTl (set) TYDb
Ternpa
c-2,
c-3,
C-4
Anilinec (95% enriched) -4 6 16 24 35 50
21.3 25.5 30.0 31.5 34.1 52.5
4.9 4.5 4.6 4.6 4.5
22 33 34 37 58
-46 +21 +43
2.3 13.2 17.5
2.1 10.8 15.4
Anilinium ion d(95% enriched) -4
0.78
6 16 24 35 50
1.1 1.5 1.6 2.2 3.1
4.0 4.4 4.8 5.1
0.97 1.1
-7
0.70
+8
1.0
1.6 1.6
-i-31
2.6
4.9
3.1
0.2 1 0.33 0.63
a Temperature in “C + 2”; measured directly on the samples. b Calculated from Tf’” = T, (obsd) . (q max/q obs). e LOMin CDCl,. d 1.0 M in CDCl, with an equivalent amount of trifuloroacetic acid plus three drops of glacial acetic acid present. e Assumed fully dipolar.
556
LEVY ET AL.
These calculated activation energies may actually be composite parameters for the processes of overall molecular reorientation and internal rotation. In fact, the observed values appear to arise largely from the overall reorientation process. This follows from the 13C T1’s for the ring carbons of aniline and the anilinium ion (Table 1). First of all, the approximate reorientational activation energies obtained from the 13C data are consistent with the more-accurate lSN-derived values. (More temperatures were used for the 15N data.) Furthermore, the relative magnitudes of 13C and lsN dipolar T1’s indicate that the NH, and NH,+ groups may be spinning at a rate comparable with the overall reorientational rate (7, 5 lo-lo set). Thus, only a small ((3 kcal mole-‘) activation energy is expected for the internal rotational motion. In the absence of internal motion, and assuming isotropic reorientation (approximated for the free amine but not actually valid for the anilinium ion’), the dipolar 15N T,‘s would be 2 and 1.3 times longer than the ring 13C Tl’s, i.e., for the NH, and NH?+ groups, respectively. Observed or interpolated 15N vs 13C Tl’s obtained on both aniline and the cation in CDCl,, in ratios of 3 : 1 to 4: 1, give evidence of some internal rotation.2 Taking into account the principal diffusion axis of the cation, and the tetrahedral geometry of the NH,+ group, it appears qualitatively that internal motion may be somewhat more restricted in anilinium trifluoroacetate (in CDCl,) than in aniline itself. This may be contrasted with behavior reported below for the dications of ovtho and mela aminobenzoic acids in strongly acidic and nonnucleophilic triflic acid solution. 15N T,‘s were also obtained on 4 A4 DMSO-d, solutions of meta- and parasubstituted anilines. In all cases dipolar relaxation was essentially complete, observed T, values being 3 to 12 sec. The more polar NO, substituent resulted in the shortest NH, T1 [3.3 set (para) and 3.9 set (meta)]. Meta-CH, andpara-Br substituents resulted in T,‘s of 6.9 and 4.9 set, respectively (versus 12.1 set for aniline itself at this concentration in DMSO-d,). Some qualitative observations were also made on the effects of paramagneti~ materials in these aniline samples. With incremental addition of Ni(acac),, incremental reduction in the T, of the amine nitrogen was observed. The NOE -was reduced effectively to zero (Tl z 0.5 see) with the addition of on& I x low4 M Ni(acac),. These results f&her emphasize the importance of reporting NOE measurements along with 15N relaxation data. Aminobenzoic Acids and Ionized Derivatives 13C and 15N chemical shifts for the ortho, meta, and para aminobenzoic acids are
presented in Table 2. Protonation of the amino group with trifluoroacetic acid (TFA) results in an upfield nitrogen chemical shift of 9 to 12 ppm. Protonation leads to ‘i’- to IO-ppm deshielding for the carbons ortho and para to the amino group and ca. 2-ppm deshielding for carbons in the meta position. Formation of the anion, by reacting the aminobenzoic acids with an equivalent amount of sodium bicarbonate in water, generally produces 13C shifts to lower fields of ’ There are insufficient nonequivalent C-H vectors in aniline to perform accurate calcuiations of overall motional anisotropy. For the anilinium ion the principal diffusion axis lies along the ring substituent axis. * In the case of the NH, group, very rapid inversion at nitrogen may also give rise to effective “N4-I dipolar relaxation, and thus this alternative mode of internal motion cannot be ruled out.
ANILINES
AND AMINOBENZOIC
557
ACIDS
TABLE 2 13C AND 15NC~~~~~~~S~~~~~
OFAMINOBENZOICACIDS
PC Solution
c-2
2-Aminobenzoic acid Neutral” Cationb Anion’ 3-Aminobenzoic acid NeutraP Cationb AnionC
115.8 124.1 117.5
4-Aminobenzoic acid Neutrala Cationb AnionC
130.9 132.8 131.9
PNd
c-3
c-4
C-5
C-6
NH,, “NH,”
115.7 123.2 119f
134.4 136.2 132.3
117.0 124.6 1201
131.9 133.7 133.0
43.5 33.6 30.3
118.7 127.5 119.6
129.7 130.7 130.1
119.5 129.2 120.7
36.9 27.8 29.4
113.5 120.8 115.5
130.9 132.8 131.9
45.7 33.9 37.4
113.5 120.8 115.5
a 4 Min DMSO-d,, relative to TMS, referenced internally to DMSO (=40X@. b 4 M in DMSO-$ with 1 equiv of CF,CO,H, referenced internally to DMSO (=40.06). c Sodium salt, 4M in D,O, referenced internally to dioxane (167.4s). d Referenced externally to a saturated aqueous NH&l solution (= 0.06). e Ring carbon chemical shifts indicate that the amine function is not protonated in either the basic or neutral solutions; protonation is effected with the stronger acid, CF,CO,H [cf. Ref. (7)l. r Assignments interchangeable.
about 1 to 3 ppm in magnitude. One exception is observed: the C-4 carbon of 2aminobenzoate is shifted upfield by 2.1 ppm. The C-4 upfield shift may be a result of an intramolecular amine-carboxylate association (see below), where additional electron density might be expected for the ring carbonpara to the carboxylare anion. It should be noted that exact comparisons of the shieldings for the anions with those observed for the cations cannot be made, since some of these observed shift differences are due presumably to solvent effects. However, it can also be seen that the shift differences are not uniform for the three anions. For the 3-amino and 4-amino sodium benzoates, the nitrogen resonance is shifted upfield by 7.5 and 8.3 ppm, respectively, while the nitrogen of the 2-amino compound is shifted upfield by almost twice that amount (13.2 ppm). The latter effect might be attributed to intramolecular ‘“salvation” interaction between the amino hydrogens and the carboxylate anion, forming a sixmembered ring: H LN/H,.. iL3 0
cko
b
The above explanation is consistent with trends in the r5N and 13C relaxation data (see below).
558
ET AL.
LEVY
13C and 15N relaxation data for the 3substituted aminobenzoic acids are given in Table 3. Comparison of the T, data for these compounds indicates that the T,‘s for the anions are much longer than those observed for the cations and neutral species. Measured macroscopic viscosities for the anion solutions in D,Q are far lower than the viscosities for the neutral acids and cations in DMSO-& However, the re~atio~s~~~ between the lower anion solution viscosities and the longer observed T,‘s is not a simple one. An order-of-magnitude increase in macroscopic viscosity lengthens the r3C Tr’s by only a factor of 2 to 5. TABLE
3
r3C Relaxation
data
“N
Relaxation
data
T, (secjd
NOEF C-d
pm 1
T, (sec)d Viscosity Solution
(cp)
2-Aminobenzoic Neutral0 Cation* AnionC
acid
3-Aminobenzoic Neutral’ Cationb Anion’ 4-Aminobenzoic Neutrala Cation* Anion’
acid
n * c d with
c-2
11 -50 4.5
26 -50 2.9
0.44 0.25 1.05
24 33 2.3
0.34 0.27 0.65
c-3
c-4
0.42 0.21 1.6
0.26 0.22 1.1
0.37 0.23 1.6
0.32 0.25 1.3
0.57 0.39 3.67
4.3 3.8 4.8
0.65 0.5 1 3.71
0.27 0.17 0.66
0.46 0.26 0.89
0.45 0.17 0.90
0.68 0.43 3.90
3.8 3.8 4.1
0.88 0.56 4.69
0.33 0.29 0.68
0.34 0.27 0.65
0.54 0.30 3.54
3.1 3.7 4.1
0.86 0.40 4.26
all samples
were
C-5 or C-6
acid
4.0 M in DMSO-d,. 4.0 M ion DMSO-d, with an equivalent Sodium salt 4.0 M in D,O. All Tr’s were measured at 40 + 2OC nitrogen prior to use.
0.33 0.29 0.68
amount
of trifluoracetic
and at a field strength
acid. of 63.1
kG;
degassed
In the neutral and acidic solutions, these aromatic carboxylic acids form well-defined dimers as a result of their ability to create two strong intermolecular hydrogen bonds, forming a favorable ring (13): the cations, in addition, have restriction on their motion
imposed by ion-solvent and ion-pair interactions. Thus the 13C Tl’s are shorter by a factor of ca. 2 for the cation of 3-aminobenzoic acid (versus the nonionized acid). contrast, the decrease in i3C T,‘s for the 2- and 4-aminobenzoic acid cations is considerably smaller. In the case of the 2substituted cation presumably the relative
ANILINES
AND AMINOBENZOIC
ACIDS
5.59
mobility results from transient internal association between the NH,+ and the C groups:
(This internal association would compete with intermolecular association of the carboxyl group.) For the 4-substituted aminobenzoic acid the small decrease in 13CT,‘s for the cation relative to the neutral acid may result from internal phenyl rotation. In basic solution, the proton of the carboxylic acid moiety is removed and thus strong carboxylic acid dimerization cannot occur. As a result, the effective molecular size is decreased, mobility increases, and longer T,‘s are observed. The relatively long 13C Ti’s observed for the 2-aminobenzoic acid anion are consistent with intramolecular %olvation” of the carboxylate group, resulting in increased overall molecular reorientation. The solution macroscopic viscosity for the anions also indicates anomolous behavior for the 2-anion. The 2aminobenzoate solution viscosity is nearly twice as high as the viscosities of the 3- and 4-anions, and yet the 2-ion mobility is increased. The 15N T, for the 2-anion is short relative to the 13C TI’s, compared with the analogous values for the 3- and 4-anions. This is also consistent with the intramolecular “solvation” picture since it indicates less NH, internal motion. Comparison of the NH, and the NH,+ dipolar Tl’s with the ring carbon Tl’s for the aminobenzoic acid derivatives (vide supra) indicates that the amino functions-do not undergo unhindered internal spinning in the nonionized acids or in the cations. However, these groups do appear to undergo rapid internal motion, which in the anions is par$icularly fast. Faster NH, group internal rotation or inversion in the anions might be due to reduced conjugation between the NH, group and the electron-rich phenyl ring of the anion. In investigating the principal axes of rotation for these molecules, the 13C Tr data indicate that the nonionized amine group has little apparent effect on the overall rotation of the molecule [as noted previously (14)l. However, when the amine group is protonated, a substantial T, decrease is observed for carbons paru to the NH3+ group. The guru carbon T, probes the slower overall motion of monosubstituted benzenes [provided that the substituent is effectively a large group (15)l while the ortho and meta carbon T,‘s can give an indication of rapid overall or internal motion around the ringsubstituent symmetry axis. Qualitative predictions can be made regarding changes of axes of rotation for the present compounds:
0.37
(estimated principal axis of diffusion shown)
0.23
560
LEVY ETAL.
From these data it is evident that the NH, group plays very little part in the overall motion of these molecules. However, upon protonation and complexation with the solvent and CF,COOcounteranion, the amino group becomes important for molecular reorientation. The ration T, (ortho or meta)lT, (para) has been shown to be a measure of the preference for anisotropic reorientation in substituted benzenes.3 This ratio can be used as a further probe of motional change induced by molecular dimerization. For 2aminobenzoic acid the ratio of Ty-3!Tp4 is 1.6. For the corresponding anion, the ratio decreases to 1.4. For the 3-aminobenzoic acid and the sodkrm benzoate derivative, the ratios (Tc-s/Ty-4) are 1.7 and 1.3, respectively. The decreases in these two sets of ratios ;l are attributed to long-lived aminobenzoic acid dimem (13) which are present in the neutral solutions but are absent for the carboxylate anions. Wications of 2- and 3-Aminobenzoic Acids
In anilinium trifluoroacetate and the aminobenzoic acid monocations, the l5 13C TI data gave little evidence for rapid spinning of the NH,+ groups. The sterically similar CF, group of toluene, by contrast, spins very rapidly with essentially zeroenergy barrier for group rotation (16,12). Two explanations for the dissimilarity of the NH,+ group internal rotation might be: (1) restriction of rotation by strong solvent or counteranion interactions, or (2) restriction of rotational motion in the equilibrating nonionized aniline (or derivative). With protonated 2- or 3aminobenzoic acid in CF,SO,H (trifiic acid, a super-acid with H,, 5 14) solution it appears that the NH,+ groups do spin rapidly. The Tr‘spectral data for diprotonated 3-aminobenzoic acid are shown in Fig. 2. This experiment, at 1 M concentration and natural abundance, required 8 h using FI
15N,NATURAL ABUNDANCE, I MOLAR, 32°C +NH3 (CF3 SO,)2
c.0
Tl -2.2sec CO2 H; I
I
ii i
1.5
1.8 '2.0 2.5 3.0 3.5 4.0 8.8
FIG. 2. Fast inversion recovery FT NMR spectra for 1.0 M m-aminobenzoic The pulse sequence repetition rate was 2.8 set; 600 scans were accumulated. 3 Higher
Tf,m/q ratios
indicate
increased
( T values in set 1
anisotropy
(see Ref. 12).
acid in CF,SO,H
(32°C).
ANILINES
AND AMINOBENZOIC
ACIDS
561
the r values exceeding 3 set had been omitted, the total experimental time for the resulting 1 A4 lsN SUPER-FIRFT experiment would have been ca. 4 br). 0
CF,SO, 0
0 CO,H
0.19
CF,SO, 0
;;J;
0.19 0.19 13C and 15N T,‘s indicated (set) liN NOEF in ( ); [All data: 32”C, 1.0 M solutions in CF,SO,Hl
The 15N dipolar T1’s for the two dications are observed to be an order of magnitude than the ring carbon Tl’s. This indicates that the rate of NH,+ group internal rotation is very rapid relative to overall reorientation of the dications in this very acidic nonnucleophilic medium. This is perhaps surprising with the 2-dication, since strong ortho steric interactions might be expected to prevent “free” rotation. To confirm the results for the dications of the aminobenzoic acids, a solvent study was undertaken for the unsubstituted anilinium ion. Table 4 lists 13C and 15N relaxation data for an&urn trifluoroacetate in several solvents. In the relatively basic or nucleophilic solvents the ratio between the o&o or meta CH carbon TI’s and the 15NH3 T, is between 1 and 2, while in CF,CO,H the analogous ratio rises above 2. In the very nonnucleophilic triflic acid tPle nitrogen/carbon T, ratio is ca. 6. It is not a simple matter to separate motional contributions for these anilinium ions quantitatively, as a result of anisotropic overall reorientation and the lack of resolution longer
TABLE 4 13C
AND
15N
T,
DATA
FOR
ANILINIUM SOLVENTS
TRIFLUOROACETATE
IN
SEVERAL
“C T, (set)
Solvent and concentration H,O (l.OM) (0.1 M) CH,OH (LOM) CH,CN (0.1 M) CH,SOCH, (1.0 M) (0.1 M) CF,CO,H (1.0 M) (0.1 M) CF,SO,H (1.0 M) (0.1 M)
ortho
meta
para
10.2 10
10.4 11 8 11.3 3.4 2.5 b b b b
5.1 5.4 5.4 5.4 1.2 1.0 b b b b
1
11.1 3.2 2.0 2.0 5 2.0 3.2
15N T, (set)
16 19 1.4 8.4 3.0 4.0 I 12 12 17
63 kG and 40°C, T,‘s i IO-15%. All relaxation dipolar. b The meta andpara resonances coincide; no calculation of T, was possible,
“At
562
LEVY ET AL.
forqml
in the CF,CO,H and CF,SO,H solvents. Nevertheless, the large increase in the nitrogen/carbon T’, ratio in CF,SO,H is qualitative proof of greatly increased internal rotation of the +NH, group. ACKNOWLEDGMENTS We gratefully acknowledge support of this research by the National Science Foundation and the Donors of the Petroleum Research Fund, administered by the American Cheniical Society. We also thank Ely Lilly and Company for a grant-in-aid. Professor Clive E. Holloway and R. C. Allen provided helpful discussion. REFERENCES 1. A. OLNSON AND E. LIPPMAA, Chem. Phys. Lett. 11,241 (197 1). 2. K. F. KUHLMANN AND D. M. GRANT, J. Chem. Phys. 55,2998 (1971). 3. J. GRANDJEAN AND P. LASZLO, Mol. Phys. 30, 413 (1975); G. C. LEVY, T. STBIGEL, J. Amer. Chem. Sot. 98,495 (1976); U. EDLLJND, C. E. HOLLOWAY,
A. HOL~K, AND A. AND G. C. LEVY, J.
Amer. Chem. Sot. 98,5069 (1976). SCHWEITZER AND H. W. SPIESS, J. Magn. Resonance 16, 243 (1974); R. A. COOPER, LICHTER, AND J. D. ROBERTS, J. Amer. Chem. Sot. 95, 3724 (1973); D. D. GI~INI, ARMITAGE, H. PEARSON, D. M. GRANT, AND J. D. ROBERTS, J. Amer. Chem. Sot. 91,3416 E. LIPPMAA, T. SALUVERE, AND S. LAISAAR, Chem. Phys. Lett 11,120 (1971). 5. G. E. HAWKES, W. M. LITCHMAN, AND E. W. RANDALL, J. Magn. Resonance 19,255 (1975). 6. D. GUST, R. B. MOON, AND J. D. ROBERTS, Proc. Nat. Acad. Sci. USA 72,4696 (1975). 7. G. C. LEVY, C. E. HOLLOWAY, R. C. ROSANSKE, J. M. HEWITT, AND C. H. BRADLEY, Org. 4. D.
R. L. I. M.
(1975);
Maen.
Resonance 8,643 (1976). 8. ?. CANET, G. C. LEVY, AND I. R. PEAT, J. Magn. Resonance 18,199 (1975). 9. J. KOWALEWSKI, G. C. LEVY, L. F. JOHNSON, AND L. PALMER, J. Magn. Resonance 10. M. SASS AND D. ZIESSOW, J. Magn. Resonance 25,263 (1977); L. F. JOHNSON,
26,533 (1977). JR., at the NATO
Advanced Study Institute in Palermo, Italy, Sept. 1976. 11. R. FREEMAN, H. D. W. HILL, AND R. KAPTEIN, J. Magn. Resonance I, 327 (1972); S. J. @ELLA, D. J. NELSON, AND 0. JARDETZKY, J. Chem. Phys. 64, 2533 (1976); R. K. HARRIS AND R. H. NEWMAN, J. Magn. Resonance 24,449 (1976). 12. G. C. LEVY, J. D. CARGIOLI, AND F. A. L. ANET,J.Amer. Chem. Sot. 94,1527 (1973). 13. G. C. LEVY AND D. TERPSTRA, Org. Magn. Resonance 8,658 (1976), and references therein. 14. G. C. LEVY, J. Magn. Resonance 8, 122 (1972); references cited in (12). 15. D. R. BAUER, G. R. ALMS, J. I. BRAUMANN, AND R. PECORA, J. Chem. Phys. 61,2255 (1974). 16. C. F. SCHMIDT AND S. I. CHAN, J. Magn. Resonance 5,151 (1971).