The Influence of Substituents on the Tautomerism of Symmetrically Substituted 2,2'-Bis-benzimidazoles

Journal of the Brazilian Chemical Society

Gesser, José C.¹  Caro, Miguel B.¹  Zucco, César¹  Dall'Oglio, Evandro¹  Universidad de Santiago de Chile, Santiago, Chile¹  Universidade Federal de Santa Catarina, Florianópolis, Brazil¹  Rezende, Marcos C.¹ 

关键词: bis-benzimidazoles;    tautomerism;    dynamic NMR;   

DOI  :  10.1590/S0103-50532002000200018

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

We have recently investigated the tautomerism of 2,2'-bis-benzimidazole in DMSO-d6 through analysis of its 1H NMR spectra at various temperatures,1 due to our interest in developing synthetic methodologies targeting these compounds.2,3 The tautomeric interconversion barrier for this class of compounds was estimated1 to be 67 kJ mol-1. The postulated mechanism essentially agreed with that proposed for the tautomerization of oxalamidines4-6 and related systems,7 which involves a stepwise proton shift and formation of intermediate dipolar species. This proton shift is accompanied by a heavy-atom reorganization of the whole molecule. The evidence for such a mechanism stemmed from isotope NMR experiments, coupled with theoretical calculations. In continuation of our interest in this subject, we decided to investigate the substituent influence on the tautomeric barriers of 2,2'-bis-benzimidazoles in solution. In contrast with related imidazole8,9 and benzimidazole10 systems, whose tautomeric processes have been studied theoretically, there are no reports on the tautomerism of substituted bis-benzimidazoles. In this paper we present the results of 1H NMR studies at various temperatures of five symmetrically substituted 2,2'-bis-benzimidazoles: 5(6),5'(6')-tetramethyl- (1); 5(6),5'(6')-dimethyl- (2); 5(6),5'(6')-dichloro- (3); 5(6), 5'(6')-dimethoxy- (4) and 4(7),4'(7')-dimethyl-2,2'-bis-benzimidazole (5). The corresponding barriers for tautomeric interconversions were calculated from the spectral variations at different temperatures and the results were interpreted by means of theoretical calculations employing the PM3 semi-empirical method.  Experimental The substituted bis-benzimidazoles were prepared by sonication of a solution of hexachloroacetone and the corresponding substituted o-phenylenediamine in ethylene glycol.11 The 1H NMR spectra of all 2,2'-bis-benzimidazoles prepared under conditions of fast exchange (N-H protons not discernible) and results of the microanalyses were as follows (chemical shifts are given in ppm): 1: d 2.45 (s, 12 H, CH3); 7.48 (s, 4 H, Ar-H). Anal. calcd. for C18H18N4: C, 74.46; H, 6.25; N, 19.30. Found: C, 74.23; H, 6.10; N, 19.18%. MS: m/z 52 (6.60), 65 (11.00), 77 (10.00), 91 (13,19), 116 (6.60), 130 (16.48), 137 (17.58),145 (18.70), 275 (27.47), 290 (100); 2: d 2.47 (s, 6H, CH3); 7.10 (d, 2 H, J 8.2 Hz, Ar-H ); 7.47 (s, 2 H, Ar-H) ; 7.55 (d, 2H, J 8.2 Hz, Ar-H). Anal. calcd. for C16H14N4: C, 73.28; H, 5.34; N, 21.37. Found: C, 73.20; H, 5.23; N, 21.32%. MS: m/z (%) 52 (15.40), 77 (26.40), 104 (9.90), 130 (27), 156 (12.08), 261 (62.64), 262 (100); 3: d 7.31 (d, 2 H, J 8.2 Hz, Ar-H); 7.72 (br s, 4 H, Ar-H). Anal. calcd. for C14H8Cl2N4 : C, 55.45; H, 2.64; N, 18.48. Found: C, 55.32; H, 2.52; N, 18.41%. MS: m/z (%) 52 (7.70), 63 (28.57), 90 (12.09), 124 (15.38), 152 (17.58), 177 (17.40), 268 (9.90), 302 (100), 303 (20.87), 304 (64.83), 305 (12.09); 4: d 3.85 (s, 6 H, OMe); 6.90 (dd, 2 H, J 8.8 Hz, J' 2.2 Hz, Ar-H); 7.14 (d, 2 H, J 2.2 Hz); 7.54 (d, 2 H, J 8.8 Hz). Anal. calcd. for C14H14N4O2 : C, 65.31; H, 4.76; N, 19.05. Found: C, 65.02; H, 4.58; N, 18.91%. MS: m/z (%) 52 (19.80), 65 (11), 77 (14.30) 91 (5.50), 147 (24.17), 236 (14.28), 251 (31.87), 279 (75.82), 294 (100); 5: d 2.65 (s, 6 H, CH3); 7.07 (d, 2 H, J 7.2 Hz); 7.18 (t, 2 H, J 7.2 Hz); 7.50 (d, 2 H, J 7.2 Hz). Anal. calcd. for C16H14N4: C, 73.28; H, 5.34; N, 21.37. Found: C, 73.14; H, 5.18; N, 21.30%. MS: m/z (%) 52 (14.29), 77 (21.98), 104 (9.90), 130 (30.77), 156 (10.00), 261 (61.54), 262 (100.00).The 1H NMR spectra were recorded with a Bruker AC-200 spectrometer, employing TMS as an internal reference and a mixture of DMSO-d6/Me2CO-d6 (1:4) as the solvent. Temperature control of the samples was achieved by calibrating the high temperature range (300-400 K) with ethylene glycol and the low temperature range (170-300 K) with methanol, following techniques described by Bruker in the Variable Temperature Unit, B-VT 2000, Manual. Before recording the NMR spectra of each sample at a specific temperature, the preset temperature was corrected according to the observed chemical shifts of 80% ethylene glycol in DMSO-d6 and 4% methanol in methanol-d6. Spectra were preliminarily recorded at various temperatures, with 10 K intervals. Near the coalescence temperatures this interval was reduced to 1 K.  Calculations Calculations in the gas phase and in solution were performed with the COSMO option12 of MOPAC 97.0. Full geometrical optimizations of the substrates and intermediates were carried out employing the PM3 hamiltonian and the eigenvector-following (EF) method of convergence. The determination of the transition state geometries was achieved by employing a transition-state-search (TS) routine, starting from different initial geometries which, in all cases, converged to the same structure. In addition, a FORCE calculation was performed for all putative ground- and transition-states. In the

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