Crystal structure of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)meth­yl]-2-(thia­zol-4-yl)-1H-benzimidazole

Hicham Gueddar; Rachid Bouhfid; El Mokhtar Essassi; Mohamed Saadi; Lahcen El Ammari

doi:10.1107/S205698901502085X

. 2015 Nov 18;71(Pt 12):o951–o952. doi: 10.1107/S205698901502085X

Crystal structure of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-2-(thiazol-4-yl)-1H-benzimidazole

Hicham Gueddar ^a,^*, Rachid Bouhfid ^a, El Mokhtar Essassi ^a,^b, Mohamed Saadi ^c, Lahcen El Ammari ^c

PMCID: PMC4719918 PMID: 26870546

Abstract

The benzimidazole ring in the title compound, C₁₆H₁₇N₃O₂S, is almost planar, with the greatest deviation from the mean plane being 0.032 (1) Å. The fused-ring system makes dihedral angles of 19.91 (7) and 24.51 (8)° with the best plane through each of the thiazol-4-yl and 1,3-dioxolan-4-yl rings, respectively; the latter exhibits an envelope conformation with the methylene C atom being the flap. Finally, the thiazol-4-yl ring makes a dihedral angle of 33.85 (9)° with the 1,3-dioxolan-4-yl ring. In the crystal, molecules are connected by a pair of C—H⋯π(imidazole) interactions to form centrosymmetric aggregates.

Keywords: crystal structure; benzimidazole; thiazol-4-yl; 1,3-dioxolan-4-yl

Related literature

For the use of the title compound as an anthelmintic, see: Brown et al. (1961 ▸); Hennekeuser et al. (1969 ▸); as a food preservative and an agricultural fungicide, see: Arenas & Johnson (1994 ▸); for induction of aneuploidy and photogenotoxicity in bacteria and cultured human cells, see: Watanabe-Akanuma et al. (2005 ▸); as an anti-angiogenic, see: Cha et al. (2012 ▸); and as a ligand for transition metal ions, see: Gueddar et al. (2013 ▸).

Experimental

Crystal data

C₁₆H₁₇N₃O₂S
M _r = 315.38
Triclinic,
a = 9.3177 (5) Å
b = 9.3786 (6) Å
c = 9.5418 (6) Å
α = 78.739 (4)°
β = 78.777 (3)°
γ = 73.632 (3)°
V = 775.95 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 296 K
0.36 × 0.31 × 0.26 mm

Data collection

Bruker X8 APEX diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▸) T _min = 0.700, T _max = 0.747
19810 measured reflections
4740 independent reflections
2804 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.116
S = 1.03
4740 reflections
199 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▸); cell refinement: SAINT-Plus (Bruker, 2009 ▸); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS2014/ (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸); software used to prepare material for publication: PLATON (Spek, 2009 ▸) and publCIF (Westrip,2010 ▸).

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S205698901502085X/tk5404sup1.cif

e-71-0o951-sup1.cif^{(671.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901502085X/tk5404Isup2.hkl

e-71-0o951-Isup2.hkl^{(377.3KB, hkl)}

Click here for additional data file.^{(6.4KB, cml)}

Supporting information file. DOI: 10.1107/S205698901502085X/tk5404Isup3.cml

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S205698901502085X/tk5404fig1.tif

Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small circles.

CCDC reference: 1435046

Additional supporting information: crystallographic information; 3D view; checkCIF report

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

Cg1 is the centroid of the N2/N3/C4/C5/C10 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13B⋯Cg1ⁱ	0.97	2.83	3.7543 (18)	160

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements, and the University Mohammed V, Rabat, Morocco, for financial support.

supplementary crystallographic information

S1. Comment

Thiabendazole [2-(4-thiazolyl)benzimidazole, TBZ], is used as a broad spectrum anthelmintic in various animals (Brown et al., 1961) and in humans (Hennekeuser et al., 1969). TBZ inhibits anaerobic respiration at the level of mitochondrial helminth-specific enzyme. This compound has also been used as a food preservative and an agricultural fungicide (Arenas and Johnson, 1994). Induction of aneuploidy and photogenotoxicity has been reported for TBZ in bacteria and cultured human cells (Watanabe-Akanuma et al., 2005). TBZ has recently been verified to be vascular disrupting agent and thus as a potential complementary therapeutic for use in combination with current anti-angiogenic therapeutics (Cha et al., 2012). TBZ is also an effective ligand to coordinate transition metal ions (Gueddar et al., 2013). The title compound is synthesized by action of TBZ on tosylated solketal under phase transfer catalysis conditions.

The molecule of the title compound is build up from fused five- and six-membered rings linked to a thiazol-4-yl cycle and, via one —CH₂— link, to a 2,2-dimethyl-1,3-dioxolan-4-yl group as shown in Fig. 1. The benzimidazole ring is essentially planar with the maximum deviation from the mean plane being 0.032 (1)° at C4 and makes dihedral angles of 19.91 (7) and 24.51 (8)° with the mean plane through the thiazol-4-yl and the 3-dioxolan-4-yl rings, respectively. The dihedral angle between the thiazol-4-yl cycle and the 3-dioxolan-4-yl ring is of 33.85 (9)°. Furthermore, the five-membered ring (O1O2C12C13C14) adopts an envelope conformations on C13 as indicated by the total puckering amplitude Q2 = 0.381 (2) Å and spherical polar angle φ2 = 72.2 (2)°. In the crystal, the molecules are held together by C13–H13B···π interactions involving the imidazole ring.

S2. Experimental

To a solution of thiabendazole (1 g, 5 × 10 ^-3 mol.) dissolved in DMF (20 ml) was added potassium carbonate (0.83 g, 6 × 10 ^-3 mol.), tetra-n-butylammonium bromide (0.13 g, 0.4 × 10 ^-3 mol) and tosylated solketal (2.79 g, 10 × 10 ^-3 mol). The mixture was heated for 48 h. After the completion of the reaction (as monitored by TLC), the inorganic material was filtered and the solvent was removed under reduced pressure. The residue obtained was recrystallized from ethanol to afford the title compound as colourless crystals.