2-(Thio­phen-2-yl)-1-(thio­phen-2-ylmeth­yl)-1H-benzimidazole

David K Geiger; H Cristina Geiger; Leo Williams; Bruce C Noll

doi:10.1107/S1600536811055103

. 2012 Jan 18;68(Pt 2):o420. doi: 10.1107/S1600536811055103

2-(Thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzimidazole

David K Geiger ^a,^*, H Cristina Geiger ^a, Leo Williams ^a, Bruce C Noll ^b

PMCID: PMC3275178 PMID: 22347034

Abstract

In the title compound, C₁₆H₁₂N₂S₂, the thiophene groups are rotationally disordered over two sets of sites, by approximately 180°, with occupancy ratios of 0.916 (2):0.084 (2) and 0.903 (2):0.097 (2). The major components of the thiophene and methylene substituted thiophene rings are canted by 24.06 (12) and 85.07 (10)°, respectively, from the benzimidazole ring system plane and the dihedral angle between the major component thiophene ring planes is 84.90 (14)°. In the crystal, there is a weak C—H⋯N hydrogen bond which links molecules into chains.

Related literature

For a discussion of the rearrangement of 1,2-diiminobenzene species to form benzimidazoles, see: Smith & Ho (1971 ▶). See Varala et al. (2007 ▶) for examples of proline-catalysed 1,2-disubstituted benzimidazole syntheses. Reich et al. (2004 ▶) provide examples of intermolecular aldimine coupling. For other syntheses of substituted benzimidazoles, see: Grimmett (1997 ▶); Bahrami et al. (2007 ▶); Du & Wang (2007 ▶). For the biological activity of benzimidazole derivatives, see: López-Rodríguez et al. (1999 ▶); Horton et al. (2003 ▶).

Experimental

Crystal data

C₁₆H₁₂N₂S₂
M _r = 296.40
Monoclinic,
a = 8.9859 (13) Å
b = 9.1601 (11) Å
c = 17.476 (3) Å
β = 93.629 (5)°
V = 1435.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.36 mm⁻¹
T = 300 K
0.80 × 0.30 × 0.10 mm

Data collection

Bruker SMART X2S benchtop diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.761, T _max = 0.965
8857 measured reflections
2527 independent reflections
1942 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.103
S = 1.05
2527 reflections
210 parameters
26 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XSHELL (Bruker, 2004 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811055103/lh5359sup1.cif

e-68-0o420-sup1.cif^{(27.2KB, cif)}

Supplementary material file. DOI: 10.1107/S1600536811055103/lh5359Isup2.mol

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811055103/lh5359Isup3.hkl

e-68-0o420-Isup3.hkl^{(124.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811055103/lh5359Isup4.mol

Supplementary material file. DOI: 10.1107/S1600536811055103/lh5359Isup5.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C16—H16⋯N2ⁱ	0.93	2.54	3.445 (4)	166

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by a Congresssionally directed grant from the US Department of Education for the X-ray diffractometer and a grant from the Geneseo Foundation.

supplementary crystallographic information

Comment

Benzimidazole derivatives are of interest because of their pharmacological uses. Examples include inhibitors of serotonin activated neurotransmission (López-Rodríguez et al., 1999) and antiviral agents (Varala et al., 2007). They have also found use as antiarrhythmic, antihistamine, antiulcer, anticancer, fungicidal, anthelmintical drugs (Horton et al., 2003).

Numerous methods are available for the synthesis of substituted benzimidazoles (Grimmett, 1997). One pot procedures for the synthesis of 2-aryl substituted benzimidazoles involving the condensation of 1,2-diaminobenzene with aldehydes employing hydrogen peroxide and ceric ammonium nitrate (Bahrami et al., 2007) or hypervalent iodine (Du & Wang, 2007) as oxidizing agents have been reported. Syntheses of 1-arylmethyl-2-aryl substituted benzimidazoles via the proline catalyzed condensation of 1,2-diaminobenzene derivatives with aryl aldehydes have also been reported (Varala et al., 2007). Attempts to prepare N,N'-dibenzal-o-phenylenediamine via the condensation of 1,2-diaminobenzene and benzaldehyde lead to presumed rearrangement of the initially formed Schiff base yielding 1-benzyl-2-phenylbenzimidazole (Smith & Ho, 1971).

Our efforts have focused on the preparation of benzimidazole analogues which have substituents capable of binding metals. Toward that end, we have prepared 1-(thiophene-2-methyl)-2-(2-thiophene)benzimidazole, TMTB, from a reaction of 1,2-diaminobenzene with 2-thiophenecarboxaldehyde.

Figure 1 shows a perspective view of TMTB with the atom-labeling scheme. Only the major components of the disordered thiophene groups are displayed. Close C—H16···N2 intermolecular interactions (2.535 Å, 165.8°) result in chains of TMTB as shown in Figure 2. Bifurcated C—H11···C14 and C15 intermolecular contacts (2.843 Å and 2.848 Å) join the chains to form a layer network (see Figure 3). Figure 4 is a perspective view of the compound showing both major and minor components of the disordered thiophene groups.

The structure exhibits the expected planar benzimidazole moiety (maximum deviation 0.0076(0.0014) Å, N1). The major components of the disordered thiophene and methylthiophene rings are canted 24.06 (12) ° and 85.07 (10) °, respectively, from the benzimidazole plane, with a thiophene-methylthiophene dihedral angle of 84.90 (14) °. Together, the thiophene groups provide a structure with the potential to behave as a bidentate ligand employing the sulfur atoms. We are exploring the coordination chemistry of TMTB.

Experimental

The title compound was prepared by the reaction of two equivalents of 2-thiophene with 1,2-diaminobenzene in the presence of a catalytic amount of aluminium trichloride under nitrogen in dichloromethane. The reaction mixture was refluxed for 8 h,filtered and the solvent removed by rotary evaporation. The crude product was purified by column chromatography (silica gel)using 20%(v/v) ethylacetate in hexanes.

The purified product was characterized via¹H and ¹³C NMR spectroscopies. ¹H NMR spectrum (DMSO-d₆, 400 MHz, p.p.m.): 8.14 (2H, m), 7.98 (1 H, m), 7.50 (2 H, m), 7.44 (1 H, m), 7.39 (1 H, m), 7.10 (1 H, m), 6.94 (1 H, m), 6.05 (2 H, s). ¹³C NMR spectrum (DMSO-d₆, 100 MHz p.p.m.): 177.15, 150.63, 143.52,138.59, 135.33, 133.05, 130.91, 129.49, 128.70, 128.01, 188.14, 117.51, 117.13, 115.37, 22.58.

Single crystals were grown via vapor diffusion of cyclohexane into a concentrated methanolic solution.