5-Bromo-2-(thio­phen-2-yl)-1-(thio­phen-2-ylmeth­yl)-1H-benzimidazole

David K Geiger; Matthew R Destefano

doi:10.1107/S1600536812042146

. 2012 Oct 13;68(Pt 11):o3123. doi: 10.1107/S1600536812042146

5-Bromo-2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzimidazole

David K Geiger ^a,^*, Matthew R Destefano ^a

PMCID: PMC3515228 PMID: 23284448

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₁₆H₁₁BrN₂S₂. In the crystal, weak C—H⋯N hydrogen bonds and C—H⋯thiophene ring interactions link the molecules into chains along [100]. The structure exhibits disorder of the 2-thiophen-2-yl substituent of one of the symmetry-unique molecules with a major:minor component ratio of 0.914 (3):0.086 (3).

Related literature

For the characterization of 2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzimidazole, see: Geiger et al. (2012 ▶). For examples of pharmacological uses of benzimidazoles, see: López-Rodríguez et al. (1999 ▶); Varala et al. (2007 ▶); Horton et al. (2003 ▶). For the synthesis of substituted benzimidazoles, see: Grimmett (1997 ▶).

Experimental

Crystal data

C₁₆H₁₁BrN₂S₂
M _r = 375.30
Monoclinic,
a = 12.6753 (17) Å
b = 10.5413 (11) Å
c = 23.581 (3) Å
β = 100.878 (4)°
V = 3094.1 (6) Å³
Z = 8
Mo Kα radiation
μ = 2.92 mm⁻¹
T = 200 K
0.60 × 0.20 × 0.10 mm

Data collection

Bruker SMART X2S benchtop diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a ▶) T _min = 0.46, T _max = 0.76
19813 measured reflections
5581 independent reflections
4191 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.091
S = 1.02
5581 reflections
392 parameters
91 restraints
H-atom parameters constrained
Δρ_max = 0.65 e Å⁻³
Δρ_min = −0.80 e Å⁻³

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

Supplementary Material

Click here for additional data file.^{(34.6KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812042146/lr2085sup1.cif

e-68-o3123-sup1.cif^{(34.6KB, cif)}

Click here for additional data file.^{(273.3KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812042146/lr2085Isup2.hkl

e-68-o3123-Isup2.hkl^{(273.3KB, hkl)}

Click here for additional data file.^{(7KB, mol)}

Supplementary material file. DOI: 10.1107/S1600536812042146/lr2085Isup3.mol

Click here for additional data file.^{(5.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812042146/lr2085Isup4.cml

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

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

Cg2 and Cg4 are the centroids of the S2,C13–C16 and S4,C29–C32 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12ⁱ—H12B ⁱ⋯N4	0.99	2.57	3.454 (4)	149
C22—H22⋯N2	0.95	2.61	3.504 (4)	158
C28—H28A⋯N2	0.99	2.61	3.522 (4)	152
C6ⁱ—H6ⁱ⋯N4	0.95	2.65	3.547 (4)	157
C3—H3⋯Cg4	0.95	2.68	3.578 (4)	158
C19—H19⋯Cg2ⁱ	0.95	2.62	3.512 (4)	157

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by a Congressionally directed grant from the US Department of Education (grant No. P116Z100020) for the X-ray diffractometer and a grant from the Geneseo Foundation.

supplementary crystallographic information

Comment

Benzimidazole derivatives have a myriad of pharmacological uses, including as inhibitors of serotonin activated neurotransmission (López-Rodríguez et al., 1999) and antiviral agents (Varala et al., 2007). They are also in antiarrhythmic, antihistamine, antiulcer, anticancer, fungicidal, and anthelmintical drugs (Horton et al., 2003).

Numerous methods are available for the synthesis of substituted benzimidazoles (Grimmett, 1997). Our efforts have focused on the preparation of benzimidazole analogues which have substituents capable of binding metals. Toward that end, we have prepared the title compound from a reaction of 1,2-diamino-4-bromobenzene with 2-thiophenecarboxaldehyde. The 5-bromo and 6-bromo substituted benzimidazoles are formed in an approximately 3:2 ratio based on ¹H NMR spectral data. However, only the 5-bromo isomer forms single crystals under the crystallization conditions employed.

Figure 1 shows a perspective view of the two molecules in the asymmetric unit with the atom-labeling scheme. The molecules exhibit the expected planar benzimidazole moieties with maximum deviations of 0.030 (3) Å (C5) and 0.026 (2) Å (C21) in molecules 1 and 2, respectively. The thiophene rings display maximum deviations from planarity of 0.0004 (23) Å (C10 and C11), 0.005 (2) Å (C16), 0.005 (4) Å (C24), and 0.007 (2) Å (C29).

Figure 2 shows the unit cell as viewed down the a axis. Chains of molecules are held together via weak C—H···N and C—H···thiophene ring interactions. The motif is shown in Figure 3. The H19···Cg2 and H3···Cg4, where Cgn refers to the centroid of the thiophene ring containing the sulfur labeled Sn, are 2.62 Å and 2.68 Å, respectively. H19 is 2.618 (3) Å from the thiophene mean plane and H3 is 2.673 (3) Å from the thiophene mean plane.

Experimental

An approximately equimolar mixture of the 5-bromo and 6-bromo derivatives of the 1,2-disubstituted benzimidazole was prepared by reaction of 500 mg 1,2-diamino-4-bromobenzenene and 0.50 ml 2-thiophenecarboxaldehyde in refluxing dichloromethane (8 ml) in the presence of a catalytic amount of aluminium trichloride for eight hours. After removal of insoluble inorganic material, the solvent was removed by rotary evaporation leaving a brown, tarry substance. The mixture was subjected to column chromatography on silica gel using a 1:4 ethylacetate:hexanes eluent. A light yellow fraction was collected. Based on the presence of two CH₂ resonances in the ¹H NMR spectrum, the 5-Br and 6-Br isomers were present in a 3:2 ratio.

Slow evaporation of a 1:4 ethylacetate:hexanes solution at 40°C yielded single crystals of the title compound suitable for X-ray diffraction. A ¹H NMR spectrum of a solution of single crystals showed that only the 5-Br isomer was present. ¹H NMR spectrum (CDCl₃, 400 MHz, p.p.m.): 7.93 (1H, s), 7.54 (1H, m), 7.48 (1H, m), 7.36 (1H, m), 7.23 (2H, m), 7.15 (1H, m), 6.85 (1H, bs), 5.68 (2H, s).