bis-(1H-Benzimidazol-2-yl)-methanone: New preparation method, crystal structure, vibrational spectroscopy and DFT calculations Fabio da Silva Miranda a, * , Fabrício Gava Menezes a , Juliano Vicente a , Adailton J. Bortoluzzi a , César Zucco a , Ademir Neves a , Norberto Sanches Gonçalves b a Departamento de Química, Universidade Federal de Santa Catarina, CP476, 88040-900 Florianópolis, SC, Brazil b Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Campus Diadema, 09972-270 Diadema, SP, Brazil article info Article history: Received 29 May 2009 Received in revised form 21 August 2009 Accepted 24 August 2009 Available online 31 August 2009 Keywords: Benzimidazole B3LYP Vibrational spectroscopy abstract This study reports a new preparation of bis-(1H-benzimidazol-2-yl)-methanone, 3, an interesting com- pound prepared by the oxidation of bis-(1H-benzimidazol-2-yl)-methane using two methods: (i) Fe(II)/ O 2 in ethanol–water and (ii) hydrogen peroxide in acetic acid. Products of both methodologies were prop- erly characterized by elemental analysis, IR, Raman, ( 1 H and 13 C) NMR and X-ray crystallography. DFT cal- culations [B3LYP/6-31+G(d,p)] also showed good agreement between the theoretical and experimental values of optimized and X-ray structures as well as between the vibrational and NMR spectroscopy. The study of the conformational dynamics of 3 found a low energy barrier (0.41 kcal mol 1 ) between the two conformations in the DMSO phase. Ó 2009 Elsevier B.V. All rights reserved. 1. Introduction Ligands containing heterocyclic aromatic units and their metal complexes have extensive applications in many types of technol- ogy. Many heterocyclic compounds containing benzimidazole units, 1 (see Scheme 1), have very interesting properties and appli- cations. Some derivatives of 1 have potent biologic activities as anti-tumor [1,2], anti-HIV [3], anti-Parkinson [4], anti-microbial [5] and anti-HCV NS3/NS4A serine protease [6], among others. Also, benzimidazoles can be used in liquid crystals [7,8], OLED’s [9–11], switch’s devices [12], DNA intercalator [1,2] and selective receptors to the PO 4 3 anion [13]. Coordination chemistry involv- ing derivatives of 1 is very well documented. A considerable num- ber of metal complexes including Co, Ni, Cu, Zn, Mn, Ag, Au, Cr and Re have had their structures and properties studied when coordi- nated with ligands containing benzimidazoles moieties [7,14– 23]. The Cu(II)-methylene-bis(N-methyl)benzimidazole is used in industry for homopolymerization and co-polymerization of olefins and acrylates [16]. Dismukes et al. reported a Mn binuclear com- pound with benzimidazoles moieties as a model to catalase [17]. Complexes of benzimidazoles with Lanthanides such as La, Pr, Eu, Gd, Tb and Yb exhibit high fluorescence [24]. Recently, Ru-phenan- throline complexes with chelant ligands containing benzimidaz- oles and sulfur were reported to have a strong DNA binding and high anti-cancer activity, being more potent than cisplatin against melanoma A375, and less toxic to normal cells [1]. Also, some bio- logical studies have shown how analogues of ketone 3 are effective as inhibitors of cell death (particularly apoprotic cell death, when administered in cell culture or in vivo) [25,26]. As part of our work in exploring both new building blocks to prepare new functional molecules and metal complexes derivates from 1, we decided to explore the chemistry of the bis-(1H-ben- zimidazol-2-yl)-methane 2 to prepare the bis-(1H-benzimidazol- 2-yl)-methanone 3. The reported method for the synthesis of 3 involves reactions of benzimidazole with formaldehyde, tert-bu- tyl lithium and carbonylimidazole [26]. It was recently reported that bis-(1H-benzimidazol-2-yl)-methane, 2, reacts with Co(II) un- der an oxygen atmosphere to afford a metal complex Co(II)-3 [23]. This means that oxidation of 2 to 3 proceeds during the metal com- plex formation. The characterization by elemental analysis, IR and X-ray crystallography revealed that ketone 3 was not isolated alone, but together with compound 2 in a ratio of 2:1 [23]. Similar to this oxidative process, the reaction of an N-methyl derivative of 3 was reported as an internal monooxygenase model [28]. In this paper we describe the synthesis of 3 by two adaptations of an oxidation procedure reported in literature. Methods are as follows: (i) iron (II)/O 2 in ethanol–water [23,27] and (ii) hydrogen peroxide in acetic acid [28]. The ketone 3 was characterized by ele- mental analyses, IR, Raman, 1 H NMR, 13 C NMR and X-ray crystal- lography. In addition, we performed structural optimization of 3 by DFT calculations and compared these results with X-ray results and simulated vibrational and NMR spectra. Compound 3 attracts our interest because of its relatively low exploration, the possibility 0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2009.08.031 * Corresponding author. Tel.: +55 48 3721 6849; fax: +55 48 3721 6850. E-mail addresses: miranda@qmc.ufsc.br, fsmqmc@gmail.com (F.d.S. Miranda). Journal of Molecular Structure 938 (2009) 1–9 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc