l3C NMRSTUDIES
OF
%SUBSTITUTED PYRIDINES
2619
Carbon-13 Nuclear Magnetic Resonance Studies of 2-Substituted Pyridines by H. L. Retcofsky and R. A. Friedel U.S. Department of the Interior, Bureau of Mines, Pittsburgh Coal Research Center, Pittsburgh, Pennsylvania (Received February 6 , 1968)
15318
Carbon-13 magnetic resonance spectra of ten %substitutedpyridines have been obtained and analyzed. Substituents included both electron-releasing and electron-withdrawing groups. Only half of the 50 carbon shieldings measured yielded substituent effects that agree, within experimental error, with those found for the corresponding monosubstituted benzenes. Differences between substituent effects on the ring carbons for the two series of compounds ranged from -4.5 to 21.1 ppm, where a positive sign means that replacement of the hydrogen atom in the 2-position of pyridine by a substituent leads to smaller paramagnetic shifts (or larger diamagnetic ones) than replacing a hydrogen atom in benzene with the same substituent. These differences were found to be most pronounced for the carbons in the 2 position and, for these carbons, to correlate well with the electronegativity of the first atom of the substituent group. Paramagnetic shifts for the C-2 carbons were found to be much smaller than expected in those cases where considerable quantities of electronic charge had been removed by strongly electronegative groups. Shieldings of the carbon atoms in the 5 position, Le., para to the substituent, were found to reflect electron release or withdrawal by substituent groups. Substituent carbon atoms directly bonded to C-2 were all found to be less shielded than the corresponding ones in 3- and 4-substituted pyridines.
Introduction Carbon-13 magnetic shieldings have been reported for various unsaturated heterocyclic molecules, in, ~ p y r r ~ l e ,as ~ cluding azines,’ J t h i ~ p h e n e f, ~~ r a n and well as selected methyl derivatives of each. Protonated diazines have also been investigated by 13C nmr spectroscopy.2 Shieldings of lacnuclei in a number of 3- and 4-substituted pyridines have recently been reported by this laboratory and constituted the first two phases of an investigation of carbon shieldings in monosubstituted p y r i d i n e ~ . ~ JWe wish here to report carbon shieldings for ten 2-substituted pyridines which constitute the third and final phase of this investigation. The primary purpose of these studies was to obtain a collection of carbon-13 nmr spectra of nitrogen-containing heterocyclic molecules to be used in spectroscopic studies of the structure of coal, coal derivatives, and coal-like materials.
Experimental Section Nuclear magnetic resonance spectra were obtained a t a spectrometer operating frequency of 15.085 MHz and were of the rapid passage dispersion mode6 variety. Details of the experimental procedure have been reported p r e v i ~ u s l y . ~All chemical shifts are designated 6, and are referred to that of carbon disulfide (6, = 0). The compounds were all obtained from commercial sources and contained only naturally occurring carbon13. 2-Aminopyridine was examined as a saturated solution in carbon tetrachloride; all other measurements were made on neat liquids. Extensive use of proton decoupling was made to facilitate assignments of spectral peaks to specific spin-spin multiplets.
Results and Spectral Assignments Magnetic shieldings of all carbon atoms in the nine
2-substituted pyridines measured in this laboratory and Lauterbur’s results’ for pyridine and 2-picoline are given in Table I. Spectral assignments are unambiguous only for C-2 carbons, since, under the experimental conditions employed, these give single line resonances in all cases except that of the 2-fluor0 compound. The large one-bond 13C-19Fspin-spin coupling constant (244 cps) plus the fact that the components of the doublet were essentially unaffected during proton decoupling experiments removed any ambiguity from this assignment. Remaining assignments were made using the method reported previously for the 3- and the 4-substituted corn pound^.^*^
Discussion Ring-Carbon Shieldings. The effects on carbon shieldings when the hydrogen atom in the 2 position of pyridine is replaced by various substituents are listed in Table 11. Also included are the corresponding ones for monosubstituted b e n ~ e n e s , ~ Jas- ~well as differences between the two sets of data. Differences are significant only w,hen they exceed the absolute value of the accumulative experimental error which is estimated to (1) P. C. Lauterbur, J . Chem. Phys., 43, 370 (1965). (2) A. Mathias and V. M. S . Gil, Tetrahedron Lett., 3163 (1965). (3) T. F. Page, T. Alger, and D . M. Grant, J . Amer. Chem. Soc., 87, 5333 (1965). (4) H. L. Retcofsky and R. A. Friedel, J . Phys. Chem., 71, 3592 (1967). (5) H. L. Retcofsky and R. A. Friedel, ibid., 72,290 (1968). (6) P. C. Lauterbur in “Determination of Organic Structures by Physical Methods,” Vol. 2, F. C. Nachod and W. D. Phillips, Ed., Academic Press Inc., New York, N . Y., 1962, p 472. (7) K. S. Dhami and J. B. Stothers, Can. J. Chem., 43, 479 (1965). (8) H. Spiesecke and W. G. Schneider, J . Chem. Phys., 35, 731 (1961). (9) R . A. Friedel and H. L. Retcofsky, J. Amer. Chem. SOC.,85, 1300 (1963).
Volume 79,Number 7 July 1968
H. L. RETCOFSKY AND R. A. FRIEDEL
2620 Table I :
1%
Magnetic Shieldings in 2-Substituted Pyridines (ppm from CS2)
Substituent
c-2
CH-3
CH-4
CH-6
CH-6
43.1 29.1 28.9 33.3 40.4 39.4
69.2 83.2 82.3 84.2 71.9 72.2
57.3 51.9 55.5 55.6 56.0 56.3
69.2 71.6 76.8 79.7 65.4 66.7
43.1 45.4 45.7 44.7 43.2 45.2
CHzCHa
41.7 29.8
68.9 71.8
54.3 57.4
70.4 71.8
43.1 43.9
Br CN CHaa
50.5 59.4 33.8
64.8 64.5 70.3
54.0 55.3 56.5
69.8 65.9 71.7
42.7 42.0 43.9
Ha F OCHa 2"
CHO COCHa
c1
Other carbons
140.6 (CH3) -0.2 (C=O) - 5 . 8 (C=O) 168.7 (CHa) 161.7 (CH2) 179.5 (CH,) 75.3 (CN) 168.6 (CH3)
Data taken from ref 1.
a
Table I1 : Substituent Effects on Ring-Carbon Shieldings in 2-Substituted Pyridines and Monosubstituted Benzenes" -A&
r -
Substituent
F OCHs 2"
CHO COCHa
c1
CHnCHa
Br CN CH: a
Pyridines (C-2)
-14.0 -14.2 -9.8 -2.7 -3.7 -1.4 -13.3 7.4 16.3 -9.3
Benzenes (C-X)
Diff
-35.1 21.1 -30.2 16.0 -19.2 9.4 -9.0 6.3 -9.3 5.6 -6.4 5.0 -16.1 2.8 5.4 2.0 15.6 0.7 -9.1 -0.2
Pyridines (CEI-3)
Benzenes (ortho)
Diff
14.0 13.1 15.0 2.7 3.0 -0.3 2.6 -4.4 -4.7 1.1
14.3 14.7 12.4 -1.2 -0.2 -0.2 2.7 -3.3 -4.3 -0.3
-0.3 -1.6 2.6 3.9 3.2 -0.1 -0.1 -1.1 -0.4 1.4
Data for monosubstituted benzenes taken from ref 4 and 7-9.
be f1.3 ppm.' Only half of the 50 measured substituent effects for the 2-substituted pyridines fall within this range. The most interesting effects were those found for the carbon atoms bearing the substituent (C-2) and those located para to the substituents (CH-5). The latter carbons are far enough removed from the substituents to preclude any significant shielding contributions from inductive or magnetic anisotropy effects of substituents. The trend in the CH-5 carbon shieldings is essentially that found for the para carbons in monosubstituted benzenes and is consistent with that expected from variations in para-carbon charge densities arising from resonance effects of the substituents. The observed shieldings for both series of compounds are nearly linearly related to Hammett's chemicalreactivity parameters (up). The substituent effects a t CH-5 for the 2-substituted pyridines are plotted against up in Figure 1. Also included in the plot are the corresponding values for the 3-substituted pyridines: i.e., those of CH-6. The plot suggests that electron The Journal of Physical Chemistry
ppm
PyriPyridines dines (CH-4) (CH-6)
Benzenes (meta)
Diff Diff (CH-4) (CH-6)
Pyridines (CH-6)
-5.4 -1.8 -1.7 -1.3 -1.0 -3.0 0.1 -3.3 -2.0 -0.8
-0.9 -0.9 -1.3 -1.2 -0.2 -1.0 -1.6 -2.2 -1.3 -0.3
-4.5 -0.9 -0.4 -0.1 -0.8 -2.0 1.7 -1.1 -0.7 -0.5
2.4 4.4 7.6 8.1 10.5 9.5 - 3 . 8 -6.0 - 2 . 5 -4.2 1.2 2.0 2.6 2.3 0.6 1.0 -3.3 -4.3 2.5 2.8
2.3 2.6 1.6 0.1 2.1 0 0.8 -0.4 -1.1 0.8
3.2 3.5 2.9 1.3 2.3 1.0 2.4 1.8 0.2 1.1
Benzenes (para)
* Carbon shieldings for 2-methylpyridine taken from ref
Diff
-2.0 -0.5 1.o 2.2 1.7 -0.8 0.3 -0.4 1.0 -0.3
1.
release or withdrawal at the para position is influenced little, if at all, by the proximity of the substituent to the heterocyclic nitrogen. With the exception of those of the formyl, acetyl, and fluoro substituents in the 2substituted compounds and the chloro substituent in the 3-substituted ones, the effects agree within experimental error with those found for the corresponding monosubstituted benzenes. Jaff 6 and Doak have concluded from studies of basicities of 3- and 4-substituted pyridines that the Hammett equation is applicable to the prediction of substituent effects on chemical r e activity of these heterocyclic aromatic compounds.1° The 13Cnmr data suggests that their conclusions can be extended to 2-substituted pyridines. The relation between CH-5 carbon shieldings and up was used to estimate a up constant for the 2-pyridyl group. The lacspectrum of 2,2'-dipyridyl was obtained for this purpose. Carbon shieldings are given in Table 111. Unfortunately, the shieldings at CH-5 (10) H. H. Jaff6 and G. 0. Doak, J . Amer. Chem. Sac., 77, 4441
(1956).
lacNMRSTUDIES O F 2-SUBSTlTUTED PYRIDINES 10
2621
0
3-Substituted
e 2-Substituted
Ln P 5
5
5
I
W U L W
k z =. W
t
o
30
Iv) m
40 50 60 70 8c BENZENES, ppm from CS,
80
3 v)
Figure 2. Magnetic shieldings of the substituted carbon atoms in 2-substituted pyridines and monosubstituted benzenes. -5
-0.6
-0.3
0
0.3
0.6
UP
.-> .s
Figure 1. Magnetic shieldings of carbon atoms para to substituents in monosubstituted pyridines us. Hammett up constants.
c
e
s -0 E
e
. I -
and CH-3 differ by only 2.7 ppm and unambiguous assignments are not possible. Nevertheless, the substituent effects are rather small (-0.2 and 2.5 ppm) and both lead to positive up constants (-0.2). Thus the lacnmr data indicate the 2-pyridyl group to be a weak to moderate electron attracting para substituent. Table 111: ‘aC Magnetic Shieldings for 2,2‘-Dipyridyl (Saturated Solution in CSZ) Carbon
So, ppm
c-2 CH-3 CH-4 CH-5 CH-6
36.3 69.0or71.7 56.2 71.7or69.0 43.3
The carbon shieldings at C-2 are of particular interest, in that the substituent effects are, with few exceptions, unusually small when compared to those found for the benzene series. For example, replacing one of the hydrogen atoms in benzene with fluorine produces a paramagnetic shift of 35.1 ppm for the carbon atom at the position of substitution. For the corresponding atom in the 2-substituted pyridine, the change in shielding is only - 14.1 ppm, a difference of more than 20 ppm. All such differences a t C-2 are either positive or, within experimental error, essentially zero. The C-2 shieldings in the pyridines are shown plotted against those of the corresponding carbons (C-X) in the benzene series in Figure 2. The solid line represents pyridine shieldings calculated by adding
Figure 3. Deviations from additivity for C-2 carbon shields in 2-substituted pyridines vs. electronegativities of the first atom of the substituent.
the substituent effects for the appropriate benzenes to the C-2 shielding in pyridine. Deviations from this line are most pronounced for resonances which are found a t low magnetic field. On the basis of linear plots between carbon shieldings and charge densities or parameters reflecting charge this behavior would suggest incorrectly that the nitrogen atom in a 2-substituted pyridine is less effective than a carbon atom in a monosubstituted benzene in withdrawing charge from an adjacent substituted carbon atom. Clearly such linear relationships are not adequate to explain the large differences in substituent effects found a t the site of substitution for the two classes of compounds. These differences do, however, correlate reasonably well with the electronegativity of the first atom of the substituent as can be seen in Figure 3; the largest differences are positive ones but are found for the most electronegative groups. (11) H. Spiesecke and mi. G . Schneider, Tetrahedron Lett., 468 (1961).
Volume 78, Number 7 July 1968
H. L. RETCOFSKY AND R. A. FRIEDEL
2622 Since the electronegativity of nitrogen is greater than that of carbon, it appears that the large withdrawal of charge from C-2 owing to the presence of a highly electronegative group as well as the presence of electronegative nitrogen, in some manner, diminishes the magnitude of the expected paramagnetic shift. These results are in agreement with the recent theoretical interpretation of carbon shieldings given in a study of carbon shieldings in six-membered ring nitrogen heterocyclics and protonated derivatives by Pugmire and Grant.12 These workers found that the paramagnetic contributions (xP's) to carbon shieldings are related to orbital charge densities (4's) and effective nuclear charge parameters (E's) according to the expression They point out that the dependence of xp upon E3 gives rise to the near-linear charge-density-chemical shift relationship proposed originally by Spiesecke and Schneider'l and by Lauterbur,13provided that the carbon atom in question is not too positive. A plot of xp os. q, prepared by Pugmire and Grant, shows that the carbon resonance will not continue to move to lower fields without bounds as electronic charge is removed but will eventually level off and then move again to higher fields as the net charge on carbon becomes highly positive. Although the lack of quantitative values of carbon atom charge densities precludes the actual calculation of shielding constants, the plot in Figure 2, by virtue of its positive slope, clearly indicates a dependence of carbon shieldings upon differences in charge density a t C-2 owing to the presence or absence of the electronegative nitrogen atom just two bonds removed from the substituent. A least-squares treatment of the data shown graphically in Figure 2 indicates that the C-2 shieldings (6pc-2) can be calculated within =t4 ppm from benzene substituent effects (ASbceX) if a correction for the electronegativity ( e ) is made as follows 8pc-2 = 14.2
+
+ 12.4~
Observed shieldings and those calculated from this equation are given in Table IV. I n 2-substituted pyridines, two positions, CH-4 and CH-6, are meta to the substituents. Spiesecke and Schneider found substituent effects a t carbon atoms meta to substituents in monosubstituted benzenes to be very small and uniform.8 The effects at CH-4 in the
The Journal of Physical Chemistry
Table IV : Calculated and Observed C-2 Carbon Shieldings in 2-Substituted Pyridines Substituent
F OCHa "2
CHO COCHs c1 CHzCHa Br CN CHa
H
Calod
&, ppm------Obsd
27.6 27.5 32.3 36.9 36.6 45.1 29.8 54.4 61.5 36.8 40.3
29.1 28.9 33.3 40.4 39.4 41.7 29.8 50.5 59.4 33.8 43.1
Diff
1.5 1.4 1.0 3.5 2.8 -3.4 0 -3.9 -2.1 -3.0 2.8
pyridines agree well with those a t the meta carbons in the benzenes, with the exception of the fluoro compound which exhibits a large negative deviation and the ethyl and chloro compounds which show small positive and negative deviations, respectively. All deviations at CH-6 are either positive or essentially zero, as was found in the case of the C-2 carbon which are also adjacent to nitrogen. The deviations at CH-6, however, show only a very rough correlation with substituent electronegativity. Substituent effects a t CH-3, ortho to substituents, are within i4 ppm of those found for the corresponding benzenes, but no trend with any unique electronic property of substituent group is apparent. Other Carbon Shieldings. Magnetic shieldings of carbon atoms which are parts of substituent groups are included in Table I. All resonances of substituent carbons which are directly bonded to C-2 are found at lower magnetic fields than the corresponding resonances in the 3- and 4- substituted pyridines.
Acknowledgments. The authors wish t o thank F. R. McDonald (Laramie PetroleumResearch Center, Bureau of Mines) for supplying some of the samples, G. P. Thompson (Pittsburgh Coal Research Center) for valuable technical assistance, and C. E. Griffin (University of Pittsburgh) for helpful discussions. We are especially indebted to Drs. D. M. Grant and R. J. Pugmire for a prepublication copy of ref 12. (12) R. J. Pugmire and D. M. Grant, J. Amer. Chem. ~ o c . ,90, 697 (1968). (13) P. C . Lauterbur, ibid., 83, 1838 (1961).
