Mathias and Overberger
3526 J . Org. Chem., Vol. 43, No. 18, 1978 Registry No.-2,3-Diaminotoluene, 2687-25-4;2-nitro-6-methylaniline, 570-24-1; ~3-[5(6)-benzimidazole]acrylicacid chloride, 66792-91-4;5(6)-chlorobenzotriazole,94-97-3. Supplementary Material Available: Table of mass spectra data for benzimidazole substituents (6 pages). Ordering information can
be found on any current masthead page.
References and Notes N. Porter and J Baldas, "Mass Spectrometry of Heterocyclic Compounds", Wiley-lnterscience,New York, N.Y., 1971. (2) P. N. Preston, Chem. Rev., 74, 279 (1974). (3) A. Maquestiau, Y. Van Haverbeke, R. Flammang, M. C. Pardo, and J. Elqusro, Org. Mass Spectrom., 9, 1188 (1974). (4) A. Maquestiau, Y. Van Haverbeke, R. Flammang, M. C. Pardo, and J. Elquero, Org. Mass Spectrom., 10, 558 (1975). (5) A. Maquestiau, Y. Van Haverbeke, R. Flammang, M. C. Pardo. and J. Elquero, Org. Mass Spectrom., 10, 313 (1975). (6) M. H. Philllps, J. Chem. SOC.,2395 (1928); 1143 (1931). (7) J. H. Beynon and R. G. Cooks, Adv. Mass Spectrom.,6, 835 (1974). (8) R. G. Cooks, I. Howe, and D. H. Williams, Org. Mass Spectrom., 2, 137
(1) Q.
(1969). (9) T. W. Shannon and F. W. McLafferty, J. Am. Chem. SOC., 88, 5021 (1966). (IO) J. L. Occolowitz, J. Am. Chem. SOC.,91, 5202 (1969). (11) A. Selva, U. Vettori. and E. Gaetani, Org. Mass Spectrom., 9, 1161 (1974). (12) D. H. Williams and R. G. Cooks, Chem. Commun., 663 (1968).
S.Meyerson and P. N. Rylander, J. Chem. Phys., 27, 901 (1957). S.Meyerson and P. N. Rylander, J. Am. Chem. SOC.,78,5799 (1958).
T. Nishiwaki, J. Chem. SOC. C, 428 (1968). S.-0. Lawesson, G. Schroll, J. H. Bowie, and R. G. Cooks, Tetrahedron,
24, 1875 (1988). D. H. Williams, R. G. Cooks, and I. Howe, J. Am. Chem. SOC.,90, 6759 (1988). S. Safe, W. D. Jamieson, and 0. Hutzinger, Org. Mass Spectrom., 6, 33 (1972). T. Nozoe, I. Makai, and I. Murato, J. Am. Chem. Soc., 76, 3352 (1954). Compound VI is the intermediate in the synthesis of V, and the mess s
F
of labeled and unlabeled derivatives were obtained. With both the S-H and 2-13C derivatives, two fragmentation pathways were observed involving com etitive loss of HCN and HNCS in which no scramblin was observed. The ! H was cleanly lost with both fragments while the 9C was lost only with the HNCS. Thus, the same two fragmentation mechanisms are observed for V and VI. H. Budziklewicz, C. Djerassi, and D. H. Williams, "Mass Spectrometry, Organic Compounds", Holden-Day, San Francisco,Calif., 1967. A. Venema, N. M. M. Nibbering, and T. J. de Boer, Org. Mass Spectrom.,
3, 1584 (1970). C. G. Overberger and L. J. Mathias, J. Polym. Sci., Po/ym. Cbem. Ed.. in press. R. C. Weast, Ed., "Handbook of Chemistry and physics", 53rd ed,Chemical Rubber Publishing Co., Cleveland, Ohio, 1972. D. J. Rabiaer and M. M. Joullie. J. Chem. SOC..915 (1964). . . (26j J. Ridd an; B. Smith, J. Chem. SOC.,1363 (1960). (27) C. G. Overberger and C. J. Podsiadly, Bioorg. Chem., 3, 16, 35 (1974). (28) C. G. Overberger, B. KSsters, and T. St. Pierre, J. Polym. Sci., Part A- 7, 5, 1987 (1967).
Carbon- 13 Nuclear Magnetic Resonance Chemical Shifts of Substituted Benzimidazoles and 1,3-Diazaazulene L. J. Mathias and C. G. Overberger* Department of Chemistry and the Macromolecular Research Center, The University of Michigan, Ann Arbor, Michigan 48109 Received November 14,1977 The I3C NMR chemical shifts of a variety of substituted benzimidazoles and two 1,3-diazaazulenesare presented. Peak assignment is made with substituent-inducedchemical shifts (SCS)and long-range13C-1H and 13C-I3C coupling constants. The SCS of benzimidazole derivatives are compared to those of benzenes. Excellent correlations of 6(C,) are observed with up and U6 for 5(6)substituents. Similar correlationsinvolving the para carbon (Cs) exhibit greater scatter than those of the 2 carbon. The 6(Cz) values also correlate well with pK., and this correlation is used to predict a pK, of 3.4 for 5(6)-acetylbenzimidazole.The 13C spectrum of 1,3-diazaazuleneis unambiguously assigned. The chemical shifts do not agree with previously calculated charge densities. The average chemical shifts of the carbocyclic carbons indicate decreasing electron density in the seven-membered ring in the series azulene, 1,3-diazaazulene,protonated 1,3-diazaazulene,and tropylium ion. The determination and assignment of 13C NMR chemical shifts is rapidly becoming routine in many laboratories. This routine use is dependent on the confirmation of shift assignments by techniques such as partial or complete coupling of carbons to hydrogens. Increases in instrument sensitivity as well as the development of gated decoupling has made the acquisition of completely coupled spectra readily feasible. The interpretation of these coupled spectra is simplified by the fact that first-order analysis is generally sufificient for determination of not only one-bond but two- and three-bond coupling constants at the resolutions normally available. These longrange coupling constants should be characteristic of specific molecular subunits as are long-range hydrogen-hydrogen coupling constants in lH NMR spectroscopy. One of the most obvious and useful examples of long-range W-1H coupling involves the methyl group. Unlike the small to negligible "-1H coupling of ring and methyl hydrogens, ring carbons exhibit large exocyclic coupling constants to methyl hydrogens. For both pyridine2 and quinoline3 derivatives, the 2J13c-1H of the ipso carbon is found to be approximately 6 Hz, while the 2 J i q - i ~of the ortho carbons generally falls between 4 and 5 Hz. These coupling constants should be
characteristic for methyl-substituted compounds and should allow ready identification of both the ipso and ortho carbon resonances in coupled spectra. Furthermore, the relatively small effect of a methyl substituent on the chemical shift of carbons other than the ipso carbon should allow identification of the 13C resonances of the unsubstituted compounds once the spectrum of the methyl derivative is assigned. Thus, the examination of the spectrum of a methyl analogue is useful for the assignment of the spectrum of the parent compounds. The l3C NMR spectrum of benzimidazole has been reported previously in comparison with the spectra of purine derivatives.4 The spectra of the benzimidazole HC1 salts and the sodium salt of the anion were also given. Protonation of either the anion or the neutral benzimidazole resulted in downfield shifts of C5,6 along with upfield shifts of Cp, C4,7, and C8,g. These characteristic protonation shifts were then applied to purine spectra to determine the site of protonation of this material.4 In this paper, we report the 13Cchemical shifts of a number of substituted benzimidazoles. The long-range coupling of methyl hydrogens is used to more completely assign the
0022-326317811943-3526$01.00/0 0 1978 American Chemical Society
J . Org. Chem., Vol. 43, No. 18, 1978 3527
Substituted Benzimidazoles and 1,3-Diazaazulene Table I. The
Chemical Shifta of Benzimidazoles and 1,3-Diazaazulenesa carbon
compound Ib 1-HClb I' IC Ig 11' 11' III' IIIC Iv
registry no.
10 or
51-17-2 614-97-1 4887-83-6 615-15-6
IVC
312-73-2
Vd
V' VI' VIP VI11 VIII'C 1x0 Xe
4887-82-5 58442-16-3 94-52-0 15852-41-2 275-94-5
xg
azulene h
2
4
5
6
7
141.46 139.58 141.95 141.41 139.6 141.69 (141.1) 141.80 140.67 152.89 152.92 (141.4) 141.50 143.72 145.18 147.15 147.48 187.09 167.83 155.90 137.7
115.41 114.44 115.64 115.87 115.5 115.28 115.57 126.23 126.75 115.14 115.49 116.88 117.29 116.98 118.05 113.63 114.14 139.16 136.14 143.16 136.7
122.87 127.29 123.23 127.52 127.6 134.23 138.38 124.07 127.85
122.87 127.29 123.23 127.52 127.6 125.79 129.40 123.70 127.56 123.11 127.38 124.78 125.80 124.09 124.09 119.38 121.08 134.79 140.20 149.53 137.2
115.41 114.44 115.64 115.87
123.11
127.38 124.78 125.80 123.23 133.14 (147.2) 1413.39 123.45 134.55 140.98 12,3.0
115.5
115.24 115.69 113.59 112.95 115.14 115.49 116.88 117.29 116.01 115.64 115.79 117.07 123.45 134.55 140.98 123.0
8 137.92 129.79 (138.5) 132.19 130.4 135.96 130.61 138.07 131.54 139.60 132.82 138.44 138.00 (132.3) 141.48 (145.1) 140.83 139.16 136.14 143.16 136.7
9
CH3
137.92 129.79 (138.5) 132.19 130.4 137.32 132.80 138.39 131.69 139.60 132.82 138.44 138.00 (137.5) 138.87 (139.3) 137.14 157.78 161.67 154.81 140.6
21.70 22.44 17.04 16.99 14.31 13.51 (119.8) 119.87 26.791 157.78 161.67 154.81 140.6
+
* In CD30D or 1:4 CD30D + CH3OH unless otherwise noted. Values reported in ref 4. In CD3COzD or 1:4 CD3COzD CHzCOzH. 1:2:2 CH3OH CDCl:< MezSO-dc. e In MezSO-dG. f 6(COCH3).g In MezSO-de 10%concentrated HCl. Reference 18.
+
+
spectra of methyl derivatives: VC-CH~ equals 6.5-8.0 and 3 J c - c ~falls ~ between 4.0 and 6.0 Hz. Substituent-induced chemical shifts are correlated with various substituent parameters and with pK,. Finally, a procedure is established for carbon identification in 13C spectra employing long-range 13C-13C coupling in enriched samples. This procedure allows unambiguous assignment of the spectrum of 1,3-diazaa:culene. Experimental Section The syntheses of the various compounds are described in the preceding paper in this series.' Carbon-13enriched sodium formate and thiourea were used to obtain enriched benzimidazoles and L3-ciazaazulene derivatives, respectively. Most of the NMR spectra were obtained with a JOEL-PFT-'100 although a Varian CFT-20 was used for several samples with identical results for overlapping data. The resolution obtained was 0.3 to 0.7 Hz for the former instrument and 1.0 Hz for the latter. Solvent mixtures of deuterated and nondeuterated materials were geners lly employed to reduce overall cost. Hydrogen-decoupledspectra were obtained in 5 min to 3 h while coupled spectra required 4 to 18 h for adequate signal acquisition of even concentrated solutions. All chemical shifts are relative to internal Me4Si or calculated with respect to Me4Si from solvent resonance frequencies reported by Levy and Nelson.5 Any values reported in parentheses are approximate due to low intensity or unresolved coupling.
Results and Discussion The compounds studied consist of the parent benzimidazole (I); three isomeric methyl benzimidazoles (11-IV); 2-trifluoromethylbenzimidazole (V); 5(6)-chloro- (VI), 5(6)-acety1(VII), 5(6)-nitrobenzimidazole (VIII); and two 1,3-diazaazulene derivatives (IX and X). Compounds 1-111 and VI-X were also prepared with 90% 13C enrichment in the 2 position and these enriched compounds are designated by a prime, e.g., 1'. The I3C chemical shifts of I and its two ions have been previously r e p ~ r t e d . ~ The 13C chemical shifts of I-X are presented in Table I for all of the solvent systems employed. The literature values for benzimidazole, protonated benzimidazole, and azulene are given for comparison. The greater solubility of the compounds studied here in methanol, acetic acid, and dimethyl sulfoxide (MezSO) led to the use of these solvents since concentrated solutions greatly facilitate acquisition of spectra. Comparison
+
I,X=H 11, X = CH, VI, x = C1 VII, X = COCH, VIII. X = NO?
H
IV, Y = CH, V, Y = CF,
I11
IX. Z = SH X, Z = H
of chemical shifts, however, must be made with the awareness that solvent and concentration changes can cause several ppm differences in chemical shift.5 Carbon assignments were initially made by application of substituent-induced chemical shifts (SCS)for monosubstituted benzenes to the shifts of the parent benzimidazole. The characteristic quartet for two- and three-bond coupling to methyl hydrogens was then used to identify the ipso and ortho carbon peaks of 11-IV in the W-lH coupled spectra. 'This technique was especially ,important for the 4(7)-methyl derivative (111') for which the chemical shifts of the C5 and C6 peaks were within 0.5 ppm of each other, as were those of C8 and Cg. The three-bond coupling to the methyl hydrogens, however, allowed ready identification of C5 and Cg, respectively. For the 2-13C-enriched derivatives, large three-bond W Y 3 C couplings through the imidazole nitrogens were observed in all cases. The much smaller two-bond couplings to the quaternary 8 and 9 carbons were not always resolved and in some cases merely resulted in peak broadening. The 4,8 and 5,7 peaks in the spectrum of X were surprisingly close together. With X', however, a doublet was observed for the 4,8 peak with 3 J 1 3 ~ - 1 3=~ 12.2 Hz. The effect of solvent on 13C chemical shift has not been extensively evaluated in the literature, although Levy and
3528
J.O>g. Chem., Vol. 43, No. 18, 1978
Mathias and Overberger
Table 11. Subsequent-Induced Chemical Shifts (SCS) of Substituted Benzimidazoles in CDsOD" substitutent
2
4
5
6
7
8
9
5-CH3 (11) 4-CH3 (111) 2-CH3 (IVj 2-CF3 (V) 5-C1 (VI) 5-COCH3 (VIIj 5-NO2 (VIIIj
-0.3 -0.2
-0.4
11.0
0.8
2.6 0.5 -0.1 1.6 0.9 0.9 -3.9
-0.4 -2.1 -0.5
-2.5 -0.4
-1.2
10.6 -0.5
1.2
1.1 -0.1
0.4
-1.0
1.1 -0.1 -6.2 0.4 0.8
10.9 -0.6
1.8 3.2 5.2
1.2 1.3 2.4 -2.0
-0.1
1.6 6.0
9.9 24.0
0.0
3.0
0.2
6.6
-
a Ppm from the corresponding carbon substituent6 of benzimidazole; positive values indicate downfield shifts. b The ipso carbon is italic.
co-workers have investigated a few benzene derivatives.5 Generally, a change of solvent does not greatly change chemical shifts (
