R. H. Cox AND A. A. BOTHNER-BY
1642
(4’)
found kj’/k4’ = 3.16 exp(800/RT) with an uncertainty of =k 1000 cal mole-1 in Est - E4t. The ratio of preexponential factors &/A4 was found to be 4.95. It is interesting to note that both the simple collision theory and the transition-state theory lead to values of about unity for that ratio. Schwarz, et al., found, by transition-state theory, that the ratio of preexponential factors (A5/A4) was 4 X However they omitted the moment of inertia of the transition state in their calculation. The inclusion of that moment of inertia loads to a value of about unity for A possible explanation for the high value found by Schwarz, et al., for k5/k4 is that the presence of mercury in their reaction system, which reacts with Iz to form HgI, may have affected their results. The ratio of the rate constants for the hot reactions ( k 2 / k l ) was found to be 4.2 =k 0.2 by Schwarz, et aLJ4 and 3.8 =k 0.3 by Williams and Ogg.3 Since the hot atoms require no energy of activation in reactions 1 and 2, it seems that the preexponential factors are essentially the same for both thermal and hot atoms.
(5’)
(8) M. C. Flowers and 5. W. Benson, J . Chem. Phys., 38,882 (1962 )
I n the presence of an adequately large excess of C 0 2 we need consider only reactions of the thermal H
+ H I H2 + I H + +H I + I
H
---+
12
(4)
(5)
which lead to the relationship
The values obtained for l e ~ / J c 4are given in Table I. AIthough the effect of temperature on k5/k4is small, it is nevertheless significant (Figure 2) and leads to k5/k4 = 4.95 exp(640/RT). Since E6 is generally regarded as being zero, E4 = 640 cal mole-’ is in general agreement with Sullivan’s5Jvalue of 480 f 350 cal mole-l but not with that of Schwarz, Williams, and Hamil14of 4500 cal mole-’. Flowers and Benson,8who competed the reactions
+ H I +CH4 + I CH3 + 1 2 CHJ + I CH3
---+
Proton Nuclear Magnetic Resonance of Di- and Trisubstituted Pyrazines and Their Cations by R. H. Cox and A. A. Bothner-By Mellon Institute, Carnegie-Mellon Universitu, Pittsburgh, Pennsylvania
15.919
(Received October 27, 1967)
The proton nmr spectra of eight substituted pyrazines in neutral and acidic solvents have been analyzed. Long-range couplings over five and seven bonds were found. Protonation effects on coupling constants are discussed. Results obtained from the analysis of compounds bearing a hydroxy substituent suggest they exist in the keto form.
Introduction The factors affecting the nmr parameters of a variety of aromatic compounds are rapidly being elucidated. Considerable effort has been devoted to substituted benzenes’-5 and pyridines,6-8 focusing on the nature of substituent effects. I n an earlier paper9 we have shown that substituent effects in monosubstituted pyrazines parallel, roughly, the effects in monosubstituted benzenes and pyridines. Also, the magnitude of the vicinal coupling constant (JS6)and the chemical shifts were shown to reflect tautomeric structures in monosubstituted pyrazines. The Journal of Physical Chemistry
By determining the effects of protonation on nmr parameters often, information regarding the site of (1) S. Castellano and C. Sun, J . Am. Chem. Soc., 88, 4741 (1966). (2) 9. Castellano, R. Kostelnik, and C. Sun, Tetrahedron Letters, in press. (3) S. Castellano, private communication. (4) J. M. Read, Jr., R. E. Mayo, and J. H. Goldstein, J . M o l . Spectry., 21, 235 (1966). (5) J. M. Read, Jr., and J. H. Goldstein, ibid., 23, 179 (1967). (6) J. B. Merry and J. H. Goldstein, J . Am. Chem. Soc., 88, 5560 (1966). (7) S. Castellano, C. Sun, and R. Kostelnik, J . Chem. Phys., 46, 327 (1967), and references therein.
PROTON NMRSPECTRA OF DI- AND TRISUBSTITUTED PYRAZINES
1643
The seven-bond long-range coupling between protons protonation and electronic redistribution within the of the two methyl groups is unambiguously shown by molecule may be obtained. Several papers have appeared in the past few years on this subject.1°-16 spin-decoupling experiments and was observed in each trisubstituted pyrazine examined. Figure 1A shows However, the main emphasis has been on chemical the normal spectrum of the methyl protons of 2-chloroshift changes, and only recently have protonation effects on coupling constants been c ~ n s i d e r e d . ~ ~3,6-dimethylpyrazine. ~ ~ ~ ~ ~ ' ~ ~ ~ ~ When proton 5 was irradiated, each of the two multiplets collapsed into quartets with The relative simplicity of the nmr spectra of 2,3equal spacing between the lines (Figure 1B). disubstituted pyraaines makes this system ideally suited to a study of protonation effects on coupling Discussion constants. In this paper, we wish to report the analysis Chemical Shifts. The use of a common solvent for all of the proton nmr spectra of four di- and three trisubcompounds was frustrated by limited solubilities. stituted pyrazines. Parameters were obtained from Comparison of chemical shifts is therefore less meaningboth neutral and acidic solutions. Protonation effects ful than in the ideal case. Nevertheless, trends are and the structure of compounds containing the poobservable, particularly in those shifts resulting from tentially tautomeric hydroxyl and amino substituents transfer from a neutral to an acidic solvent. are discussed.
Experimental Section Materials. 2-nlethoxy-3-methylpyrazine(bp 70" (25 mm)) and 2-methoxy-3,6-dimethylpyrazine(bp 85" (27 mm)) were prepared from the chloro compounds by a modification of the procedure given for 2-methoxypyrazinealg The remainder of the compounds were of commercial origin. Liquids were further purified by vacuum distillation. Crystalline solids were used as received. Solvents were reagent grade or better. No impurity peaks could be observed in any of the spectra obtained. Samples were made up gravimetrically to 10 mole % of a solution containing 2% tetramethylsilane serving as internal reference and lock signal source. All samples were degassed and sealed under vacuum. To avoid the effects of decomposition with acidic solutions, all samples were run within 24 hr of preparation. Spectra. Varian Associates A-60 and HA-100 spectrometers were used to obtain the proton nmr spectra. Frequency-sweep spin-decoupling experiments were performed using a Hewlett-Packard 201CR audiooscillator monitored by a Varian V-4315 frequency counter. Calibration of spectra was by the side-band method. Line positions were obtained by averaging the results of two upfield and two downfield scans. Scan widths of 50 Ha were employed with sweep times of 500 and 1000 sec for the A-60 and HA-100, respectively.
Results Analysis of the simple AB pattern presented by the aromatic protons of disubstituted pyrazines was carried out in the usual manner.20 Long-range couplings to the protons of the methyl group were obtained from a first-order analysis of the methyl proton signals. Parameters obtained from the analysis are given in Table I. Although no coupling between the methyl protons and proton 6 could be resolved, a coupling was indicated since the signals from proton 6 became narrower when the methyl signals were irradiated.
n
Figure 1. Proton nmr spectrum of the methyl protons of 2-chloro-3,6-dimethylpyrazinein chloroform-d solution at 100 MHa: ( A ) normal spectrum and (B) proton 6 irradiated spectrum. (8) S. Castellano and R. Kostelnik, J . Am. Chem. Soc., in press. (9) R . H. Cox and A. A. Bothner-By, J . Phys. Chem., in press. (10) J. M. Read, Jr., and J. H. Goldstein, J . Am. Chem. Soc., 87, 3440 (1965). (11) G. B. Barlin and W. V. Brown, J . Chem. Soc., Sect. B , 648 (1967). (12) S. Castellano, H. Gunther, and S. Ebersole, J . Phys. Chem., 69, 4166 (1965). (13) G . B. Barlin and T. J. Batterham, J. Chem. Soc., Sect. B, 516 (1967). (14) H. Kamei, J . Phys. Chem., 69, 2791 (1965). (15) A. Mathias and V. M. S. Gil, Tetrahedron Letters, 3163 (1965). (16) R. L. Hinman and E. B. Whipple, J . Am. Chem. Soc., 84, 2534 (1962). (17) M. H. Palmer and B. Semple, Chem. Ind. (London), 1766 (1965). (18) K. Tori, M .Ohtsuru, K. Aono, Y. Kawazoe, and M. Ohnishi, J . Am. Chem. Soc., 89, 2765 (1967). (19) A. Albert and J. N. Phillips, J . Chem. SOC.,1294 (1956). (20) J. A . Pople, W. G. Schneider, and H. J. Bernstein, "HighResolution Nuclear Magnetic Resonance," McGraw-Hill Book Co., Inc., New York, N. Y., 1959, p 119.
volume 72, Number 6
May 1988
R. H. Cox AND A. A. BOTHNER-BY
1644 Table I : Nmr Parameters of Substituted Pyrazines
Substituents
2-CHa, 5-CH3 2-OH, 3-CH3 2-NH%,3-CH3 2-OCH3, 3-CH3 2-C1, 3-CHa 2-OH, 3-CH3, 6-CH3 2-OCH3, 3-CH3, 6-CH3 2-C1, 3-CH3, 6-CH3
Solvent"
CDCl3 TFA DMSO TFA DMSO TFA DMSO TFA CDCls TFA CDCla TFA CDCls TFA CDCls TFA
6sb
2 . 507d 2.941d
... ... 6 . 117d
...
3 .935d 4.266d
...
... ... ... 3 . 93gd 4 . 224d
...
. . *
6a
66
8.330 9.014 2 . 28jd 2 . 88gd 2 . 32gd 2 . 854d 2 . 39gd 2 . 79gd 2 . 657d 3.011d 2 . 296d 2 . 572d 2 . 385d 2 . 670d 2 . ZOOd 2 . 823d
60
2 . 507d 2.941d 7.250 8.078 7.786 8.149 8.020 8.716 8.202 8.711 7.154 7.423 7.826 7.920 8.240 8.513
8.330 9.014 7.166 7.602 7.641 8.076 8.041 8.093 8.378 9.045 2 .414d 2 ,79gd 2 . 403d 2 . 713d 2 59gd 2 . 934d I
'
a DMSO = dimethyl sulfoxide, TFA = trifluoroacetic acid. I n ppm downfield from TMS. stant of met,hyl or methoxyl protons a t the given numbered position.
!
Chemical shifts of the ring protons in disubstituted pyrazines are very similar to the corresponding shifts in monosubstituted pyrazines. Introduction of a methyl group produces an upfield shift of -0.2 ppm for the ring protons, compared to the corresponding shifts in the monosubstituted p y r a ~ i n e s . ~Furthermore, the 3-methyl group causes a reversal in the order of appearance of the ring protons from that found in monosubstituted pyrazines. For n-electron-donating groups, proton 6 appears at higher field, whereas for n-electronwithdrawing groups, proton 5 appears at higher field. At present, the factor(s) responsible for this reversal is (are) not apparent. In trifluoroacetic acid, pyrazine at concentrations less than 0.2 M is completely pr0t0nated.I~ Upon protonation of the disubstituted pyrazines, the ring protons are shifted to lower field by 0.45-0.75 ppm and the protons of the 3-methyl group are shifted to lower field by 0.35-0.60 ppm. For the trisubstituted pyrazines, the ring proton is shifted to lower field by 0.1-0.25 ppm and the protons of the methyl groups are shifted by 0.3 ppm. These protonation shifts are similar to those found in pyrazine,l* pyridine16 and substituted pyridines.8 The downfield shifts are approximately identical for protons 5 and 6 of the disubstituted pyrazines suggesting equal protonation of both nitrogens. An exception to the shifts observed for disubstituted pyrazines is proton 6 of 2-methoxy-3-methylpyrazine which is shifted downfield by only 0.05 ppm. One possible explanation for this small shift is that a positive charge on nitrogen-1 could be stabilized by resonance with the 2-methoxy group. The Journal of Physical Chemistry
Ja6'
JM
... ...
...
0 , 64d 0 ,72d 0 . 66d (
