2-({4-[4-(1H-Benzimidazol-2-yl)phen­yl]-1H-1,2,3-triazol-1-yl}meth­oxy)ethanol

Abdelaaziz Ouahrouch; Moha Taourirte; Hassan B Lazrek; Jan W Bats; Joachim W Engels

doi:10.1107/S1600536812023410

. 2012 May 26;68(Pt 6):o1908. doi: 10.1107/S1600536812023410

2-({4-[4-(1H-Benzimidazol-2-yl)phenyl]-1H-1,2,3-triazol-1-yl}methoxy)ethanol

Abdelaaziz Ouahrouch ^a, Moha Taourirte ^a, Hassan B Lazrek ^b, Jan W Bats ^c,^*, Joachim W Engels ^c

PMCID: PMC3379465 PMID: 22719663

Abstract

In the title molecule, C₁₈H₁₇N₅O₂, the dihedral angle between the benzene plane and the benzimidazole plane is 19.8 (1)° and the angle between the benzene plane and the triazole plane is 16.7 (1)°. In the crystal, molecules are connected by O—H⋯N hydrogen bonds, forming zigzag chains along the c-axis direction. The chains are connected by bifurcated N—H⋯(N,N) hydrogen bonds into layers parallel to (100). These layers are connected along the a-axis direction by weak C—H⋯O contacts, forming a three-dimensional network.

Related literature

For the bioactivity of benzimidazoles, see: Tebbe et al. (1997 ▶); Andrzejewska et al. (2002 ▶); Navarrete-Vázquez et al. (2003 ▶); Terzioglu et al. (2004 ▶); Özden et al. (2005 ▶). For the bioactivity of 1,2,3-triazoles, see: Chen et al. (2000 ▶); Manfredini et al. (2000 ▶). For the synthetic methods, see: Huisgen (1963 ▶); Crisp & Flynn (1993 ▶); Wu et al. (2004 ▶); Navarrete-Vázquez et al. (2007 ▶); Krim et al. (2009 ▶). graphic file with name e-68-o1908-scheme1.jpg

Experimental

Crystal data

C₁₈H₁₇N₅O₂
M _r = 335.37
Monoclinic,
a = 10.4449 (5) Å
b = 7.7754 (4) Å
c = 20.2119 (10) Å
β = 99.354 (1)°
V = 1619.65 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 170 K
0.40 × 0.32 × 0.11 mm

Data collection

Siemens SMART 1K CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2000 ▶) T _min = 0.953, T _max = 0.990
15768 measured reflections
3295 independent reflections
2562 reflections with I > 2σ(I)
R _int = 0.047

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.102
S = 1.14
3295 reflections
235 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: SMART (Siemens, 1995 ▶); cell refinement: SAINT (Siemens, 1995 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812023410/nc2282sup1.cif

e-68-o1908-sup1.cif^{(26.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812023410/nc2282Isup2.hkl

e-68-o1908-Isup2.hkl^{(161.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812023410/nc2282Isup3.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
N1—H1A⋯N4ⁱ	0.89 (2)	2.50 (2)	3.244 (2)	141.7 (17)
N1—H1A⋯N5ⁱ	0.89 (2)	2.21 (2)	3.088 (2)	170.4 (19)
O2—H2A⋯N2ⁱⁱ	0.92 (3)	1.85 (3)	2.761 (2)	171 (2)
C15—H15A⋯O2ⁱⁱⁱ	0.95	2.54	3.271 (2)	134
C16—H16A⋯O2ⁱⁱⁱ	0.99	2.54	3.258 (2)	129
C17—H17B⋯O1^iv	0.99	2.35	3.279 (2)	155

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

supplementary crystallographic information

Comment

Benzimidazoles are important pharmacophores in modern drug discovery (Tebbe et al., 1997). They are present in various bioactive compounds, possessing, e.g. antiparasitic (Navarrete-Vázquez et al., 2003), antimicrobial (Özden et al., 2005), antihistaminic (Terzioglu et al., 2004) and antitumor (Andrzejewska et al., 2002) activities. In addition, 1,2,3-triazoles are potent antibacterial (Chen et al., 2000) and antiproliferative (Manfredini et al., 2000) agents. The most widely used method for their synthesis is the Huisgen 1,3-dipolar cycloaddition of alkynes with organic azides (Huisgen, 1963). Copper-catalyzed click chemistry, involving azides and terminal acetylenes, has enabled practical and efficient preparation of 1,4-disubstituted 1,2,3-triazoles, from a wide range of substrates with excellent selectivity (Wu et al., 2004). In connection to our previous studies on the synthesis of acyclonucleosides (Krim et al., 2009), we decided to explore the feasibility of the click chemistry for the synthesis of novel 1,2,3-triazoles containing a benzimidazole moiety coupled via a benzene ring. Thus the title compound was prepared and its crystal structure is reported herein.

A view of the molecular structure of the title compound is shown in Fig. 1. The molecule contains three planar parts: the benzimidazole, the benzene and the triazole groups. The angle between the benzene and benzimidazole planes is 19.8 (1)°, while the angle between the benzene and triazole planes is 16.7 (1)°. The (2-hydroxyethoxy)methyl group points away from the triazole plane [torsion angle N4—N3—C16—O1: 88.6 (2)°]. The C16—O1 bond has a gauche conformation, while the O1—C17 and the C17—C18 bonds have trans conformations.

The molecules of the title compound are connected by intermolecular O—H···N hydrogen bonds to form zigzag chains along the c axis direction (Fig.2, Table 1). Adjacent molecules in each chain are related by c-gilde plane symmetry. Neighboring chains are connected by intermolecular N—H···N hydrogen bonds between imidazole and triazole groups to form layers parallel to (1 0 0). The N—H···N hydrogen bond is bifurcated with both atoms N4 and N5 acting as acceptor atoms. There are two symmetry-related N—H···N bonds between each pair of molecules. The hydrogen bonded layers are connected along the a axis direction by additional intermolecular weak C—H···O contacts to form a three-dimensional framework.

Experimental

The title compound has been prepared in four steps starting from 4-[(trimethylsilyl)ethynyl]benzaldehyde. The starting material was reacted with benzimidazole in the presence of sodium metabisulfite using microwave irradiation (Navarrete-Vázquez et al., 2007). The resulting product was deprotected with tetrabutylammonium fluoride in tetrahydrofuran to 2-(4-ethynylphenyl)-1H-benzimidazole (Crisp & Flynn, 1993). Cycloaddition of the latter product with [(2-acetoxyethoxy)methyl]azide in the presence of CuI, followed by deprotection of the acetyl group (Krim et al., 2009), afforded the title compound in good yield. The crude product was purified by passing through a column packed with silica gel. Single crystals suitable for X-ray analysis were obtained by slow recrystallizion from ethanol. The melting point is approximately 502–504 K.