¹H and ¹³C NMR spectra of condensed benzimidazole and imidazobenzodiazepines

1 Introduction

The benzimidazole nucleus and its derivatives are known to play extremely crucial roles in the structures and functions of a number of biologically important molecules, generally by virtue of their being coordinated to metal ions. The incorporation of the benzimidazole nuclei is an important synthetic strategy in drug discovery (Townsend, 1976). The high therapeutic properties of the related drugs have encouraged the medicinal chemists to synthesize the large number of novel chemotherapeutic agents (Kleeman et al., 1999). Pharmaceutical properties including: antiviral (Cheng et al., 2005), antitumoral (Yang et al., 2009; Charlson et al., 1973), antifungal and antimycotic (Walker et al., 1978), antihistaminic and antiallergic (Nakano et al., 2000), antimicrobial (Marquis et al., 2006), antihelminthic (Mavrova, 2006) and spasmolytic activity (Navarrete-Vázquez et al., 2006). These different applications have attracted many experimentalists and theorists to investigate the spectroscopic and structural properties of benzimidazole (Mohan, 1991; Klots et al., 1997; Morsy et al., 2002) and some of its derivatives (Yurdakul and Yilmaz, 1999).

In this work, we report the study of NMR spectra of condensed benzimidazoles. We have previously described the synthesis of 4-(2,5,6-trimethyl-¹H-benzo[d]imidazol-7-ylamino)pent-3-en-2-one 1a, ethyl 3-(2,5,6-trimethyl-¹H-benzo[d]imidazol-7-ylamino)but-2-enoate 1b, 4-acetonylidene-5-acetyl-2,6,8,9-tetramethyl-7H-imidazo-[1,5,4-e,f][1,5]-benzodiazepine 2a and 4-acetonylidene-5-ethoxycarbonyl-2,6,8,9-tetramethyl-7H-imidazo-[1,5,4-e,f][1,5]-benzodiazepine 2b (El kihel et al., 2008). The NMR parameters of these heterocycles are reported in this paper.

2 Results and discussion

A variety of works are reported about the NMR of benzimidazole derivatives (Embrey and Craik, 1995; Infante-Castillo et al., 2008; El kihel et al., 2005) The ¹³C NMR spectra and the charge density of carbon for the benzimidazole were reported by Pugmire and Grant (1971). The chemical shifts of carbon 13 for some benzimidazoles substituted in position 5 were published (Mathias and Overberger, 1978; Fruchier et al., 1980; Blackburn et al., 1982; Lopyrev et al., 1981, 1985). Other works have reported the NMR of some bisbenzimidazoles and condensed benzimidazoles (Dall’Oglio et al., 2002; Alcade et al., 1991; Goljer et al., 1985). After the study of the behavior of the ¹³C NMR spectra in the benzimidazole series (Goljer et al., 1985), we are interested to report our contribution in this area by using NMR spectroscopy for the elucidation of carbon13 chemical shifts of these benzimidazole derivatives. We have studied the influence of the substituents on the ¹³C NMR spectra of these compounds. The complete assignment of the resonances of the ¹³C NMR spectra of the benzimidazole derivatives was carried out by selective decoupling, NOE, and H, C-COSY experiments (see Figs. 1 and 2).

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Figure 1

The numbering of the compunds for the ¹HNMR assignments.

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Figure 2

The numbering of the compounds for the ¹³CNMR assignments.

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3 Results and discussion

Tables 1 and 2 give the ¹H and ¹³C NMR data, respectively; of 1a, 1b, 2a and 2b.

The benzimidazole presents a rapid tautomerism which does not allow to obtain all expected signals in the ¹³C NMR spectra in the case of substituted benzimidazoles by heterocycles(El Kihel et al., 2005).

This phenomenon was not observed for the open chain intermediates 1a and 1b or the condensed benzimidazoles 2a and 2b, the ¹³C NMR spectra of these compounds present all the expected signals.

For the condensed benzimidazoles as imidazobenzodiazepines, we have studied the chemical shifts of vinyl and carbonyl group in order to see the effect of conjugated system.

For the ¹³C NMR spectra of compounds 2a and 2b, the conjugated system induces a systematic shielding of the carbonyl group in position 20 (δ = 173.3 ppm for compound 2a and δ = 174.1 ppm for compound 2b) by comparison of the chemical shifts of the carbonyl group in position 15 (δ = 194.4 ppm for compound 1a and δ = 204.1 ppm for compound 2a) while the same observation applies to the carbonyl group of ester with less shielding (δ = 169.7 ppm for compound 1b, δ = 166.8 ppm for compound 2b). We also noted the deshielding of vinyl group CH in compounds 2a and 2b (δ = 105.1 ppm for compound 2a and δ = 116.6 ppm for compound 2b) by comparison of that in compounds 1a and 1b (δ = 95.8 ppm for compound 1a and δ = 83.0 ppm for compound 1b).

4 Experimental section

All compounds were characterized by their ¹H NMR and ¹³C NMR spectra as well as by microanalysis or HRMS spectra. NMR spectra were recorded on Bruker ARX 200 (200 MHz for ¹H and 50.3 MHz for ¹³C) spectrometer (Ω-ppm/TMS, J-Hz); for ¹³C NMR, the multiplicities were determined through DEPT.