Ethyl 1-[2-(morpholin-4-yl)eth­yl]-2-[4-(trifluoro­meth­yl)phen­yl]-1H-benzimid­azole-5-carboxyl­ate

Yeong Keng Yoon; Mohamed Ashraf Ali; Tan Soo Choon; Madhukar Hemamalini; Hoong-Kun Fun

doi:10.1107/S1600536811014619

. 2011 Apr 29;67(Pt 5):o1215. doi: 10.1107/S1600536811014619

Ethyl 1-[2-(morpholin-4-yl)ethyl]-2-[4-(trifluoromethyl)phenyl]-1H-benzimidazole-5-carboxylate

Yeong Keng Yoon ^a, Mohamed Ashraf Ali ^a, Tan Soo Choon ^a, Madhukar Hemamalini ^b, Hoong-Kun Fun ^b,^*,^‡

PMCID: PMC3089142 PMID: 21754513

Abstract

In the title compound, C₂₃H₂₄F₃N₃O₃, the morpholine ring adopts a chair conformation. The benzimidazole ring is approximately planar, with a maximum deviation of 0.028 (1) Å for one of the unsubstituted C atoms. The benzimidazole ring makes dihedral angles of 35.66 (4) and 75.45 (5)° with the attached phenyl and morpholine rings, respectively. In the crystal structure, adjacent molecules are linked via C—H⋯F and C—H⋯O hydrogen bonds to form a two-dimensional network.

Related literature

For background to benzimidazoles, see: Boruah & Skibo (1994 ▶); Haugwitz (1982 ▶); Hisano (1982 ▶); Hubschwerlen (1992 ▶); Shi (1996 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₃H₂₄F₃N₃O₃
M _r = 447.45
Triclinic,
a = 10.1463 (2) Å
b = 10.5595 (2) Å
c = 11.5775 (2) Å
α = 96.868 (1)°
β = 109.638 (1)°
γ = 110.833 (1)°
V = 1050.83 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 100 K
0.51 × 0.33 × 0.19 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.945, T _max = 0.979
22546 measured reflections
6122 independent reflections
5266 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.106
S = 1.03
6122 reflections
290 parameters
H-atom parameters constrained
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811014619/hb5849sup1.cif

e-67-o1215-sup1.cif^{(23.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014619/hb5849Isup2.hkl

e-67-o1215-Isup2.hkl^{(299.6KB, hkl)}

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
C2—H2A⋯F1ⁱ	0.95	2.51	3.4617 (15)	175
C10—H10A⋯O3ⁱⁱ	0.95	2.38	3.1889 (14)	143
C20—H20A⋯O2ⁱⁱⁱ	0.99	2.52	3.4878 (14)	166

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

Acknowledgments

YKY, MAA and TSC thank the Universiti Sains Malysia, Penang, for providing research facilities. HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for Research University grant No. 1001/PFIZIK/811160. MH also thanks Universiti Sains Malaysia for a postdoctoral research fellowship.

supplementary crystallographic information

Comment

A wide variety of benzimidazole derivatives have been described for their chemotherapeutic importance (Boruah & Skibo, 1994). The synthesis of novel benzimidazole derivatives remains an important focus in medicinal research. Recent observations suggest that substituted benzimidazoles and heterocyclic, which are the structural isosters of nucleotides owing to their fused heterocyclic nuclei in their structures that allow them to interact easily with the biopolymers, possess potential activity with lower toxicities in the chemotherapeutic approach in man (Haugwitz, 1982; Hisano, 1982). Moreover, these fused heterocylces were distinctively studied for their antitumor, antiviral and antimicrobial activities as new nonnucleoside topoisomerase I poisons, human immunodeficiency virus-1 reverse transcriptase inhibitors and or potent DNA gyrase inhibitors (Hubschwerlen, 1992; Shi, 1996). In addition, benzimidazole derivatives have played a crucial role in the theoretical development of heterocyclic chemistry and are also used extensively in organic synthesis.

The molecular structure of the title compound, (I), is shown in Fig. 1. The benzimidazole (N1–N2/C1–C7) ring is approximately planar with maximum deviation of 0.028 (1) Å for atom C4. The morpholine (N3/O3/C20–C23) ring adopts a chair conformation [Q = 0.5778 (12) Å, θ = 178.81 (12)°, φ = 128 (5)°; Cremer & Pople, 1975]. The central benzimidazole (N1–N2/C1–C7) ring makes dihedral angles of 35.66 (4)° and 75.45 (5)° with the attached phenyl (C8–C13) and the morpholine (N3/O3/C20–C23) rings, respectively.

In the crystal (Fig. 2), adjacent molecules are connected via intermolecular C2—H2A···F1, C10—H10A···O3 and C20—H20A···O2 (Table 1) hydrogen bonds to form a two-dimensional network.

Experimental

Ethlyl-3-amino-4-(morpholinoethylamino) benzoate (0.01 mol) and sodium metabisulfite adduct of trifluromethyl benzaldehyde (0.01 mol) were dissolved in DMF. The reaction mixture was refluxed at 130°C for 4 h. After completion, the reaction mixture was diluted in ethyl acetate (20 ml) and washed with water (20 ml). The organic layer was collected, dried over Na₂SO₄ and the evaporated in vacuo to yield the product. The product was recrystallised from ethyl acetate to yield colourless blocks of (I).