Ethyl 1-[2-(morpholin-4-yl)eth­yl]-2-[4-(morpholin-4-yl)phen­yl]-1H-1,3-benzimidazole-5-carboxyl­ate

Yeong Keng Yoon; Mohamed Ashraf Ali; Rusli Ismail; Mohd Mustaqim Rosli; Hoong-Kun Fun

doi:10.1107/S1600536811023294

. 2011 Jun 22;67(Pt 7):o1772. doi: 10.1107/S1600536811023294

Ethyl 1-[2-(morpholin-4-yl)ethyl]-2-[4-(morpholin-4-yl)phenyl]-1H-1,3-benzimidazole-5-carboxylate

Yeong Keng Yoon ^a, Mohamed Ashraf Ali ^a, Rusli Ismail ^a, Mohd Mustaqim Rosli ^b, Hoong-Kun Fun ^b,^*,^‡

PMCID: PMC3152030 PMID: 21837149

Abstract

The asymmetric unit of the title compound, C₂₆H₃₂N₄O₄, consists of two independent molecules. In both molecules, the ethoxy groups are each disordered over two sets of sites with occupancies of 0.695 (4):0.305 (4) and 0.877 (2):0.123 (2). The dihedral angles between the benzimidazole ring system and the adjacent benzene ring in the two molecules are 41.41 (5) and 31.46 (5)°. In the crystal, molecules are linked by C—H⋯O and C—H⋯N interactions.

Related literature

For biological activity of benzimidazole derivatives, see: Vijaya et al. (2009 ▶); Haugwitz (1982 ▶); Hisano (1982 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₆H₃₂N₄O₄
M _r = 464.56
Monoclinic,
a = 10.3595 (3) Å
b = 20.6870 (6) Å
c = 23.7904 (7) Å
β = 112.839 (2)°
V = 4698.7 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.50 × 0.27 × 0.14 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.957, T _max = 0.987
100050 measured reflections
20532 independent reflections
13488 reflections with I > 2σ(I)
R _int = 0.042

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.154
S = 1.02
20532 reflections
667 parameters
78 restraints
H-atom parameters constrained
Δρ_max = 0.45 e Å⁻³
Δρ_min = −0.34 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 datablock(s) global, I. DOI: 10.1107/S1600536811023294/is2728sup1.cif

e-67-o1772-sup1.cif^{(44.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811023294/is2728Isup2.hkl

e-67-o1772-Isup2.hkl^{(1,003.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811023294/is2728Isup3.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
C14B—H14D⋯O4Aⁱ	0.99	2.39	3.1322 (17)	132
C16B—H16C⋯O1Bⁱⁱ	0.99	2.42	3.2944 (15)	147
C17B—H17C⋯O3Aⁱⁱⁱ	0.99	2.60	3.4963 (18)	151
C23B—H23D⋯O2A^iv	0.99	2.53	3.3839 (16)	144
C24B—H24D⋯N1B^v	0.99	2.61	3.4668 (14)	145
C25B—H25C⋯N3A	0.99	2.61	3.5189 (18)	153

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

Acknowledgments

The authors wish to express their thanks to Universiti Sains Malaysia (USM), Penang, Malaysia, for providing research facilities. HKF also thanks USM for the Research University Grant (No. 1001/PFIZIK/811160).

supplementary crystallographic information

Comment

The benzimidazole nucleus is an important heterocyclic ring because of its synthetic utility and broad range of pharmacological activities. Benzimidazole derivatives exhibit different pharmacological effects, including antifungal. In recent years, attention has increasingly been given to the synthesis of benzimidazole derivatives as a source of new antimicrobial agents (Vijaya et al., 2009). Recent observations suggest that substituted benzimidazoles and heterocyclic, which are the structural isosters of nucleotides owing to the 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).

In the asymmetric unit (Fig. 1) of the title compound there are two molecules. In both molecules, the ethoxy group were disordered over two position with the refined occupancies of 0.695:0.305 and 0.877:0.123, respectively, for the molecules A and B. The benzimidazole (N1/N2/C1–C7) ring in both molecules is planar with the maximum deviation of 0.0129 (12) from atom C5A and -0.0246 (12) from atom C2B. It makes dihedral angles of 41.41 (5)° and 31.46 (5)° with the adjacent benzene ring, respectively, for molecule A and B. All the four morpholine rings, O2A/N3A/C23A–C26A, O3A/N4A/C14A–C17A, O2B/N3B/C23B–C26B and O3B/N4B/C14B–C17B, adopt chair conformations with [Q = 0.5722 (13)Å, θ = 1.51 (13)° & φ = 127 (5)°], [Q = 0.5411 (12)Å, θ = 8.99 (12)° & φ = 354.4 (9)], [Q = 0.5787 (12)Å, θ = 177.48 (12)° & φ = 58 (3)] and [Q = 0.5389 (14)Å, θ = 170.19 (14)° & φ = 182.8 (10)°], respectively.

In the crystal structure, molecules A and B are linked by C25B—H25C···N3A hydrogen bond. The molecules are further linked by C14B—H14D···O4Aⁱ, C17B—H17C···O3Aⁱⁱⁱ, C23B—H23D···O2A^iv and C24B—H24D···N1B^v hydrogen bonds (Table 1) to form layers that are connected by a C16B—H16C···O1Bⁱⁱ interaction (Fig. 2).

Experimental

Ethlyl-3-amino-4-(morpholinoethylamino) benzoate (0.01 mol) and sodium metabisulfite adduct of 4-morpholino benzaldehyde (0.01 mol) were dissolved in DMF. The reaction mixture was refluxed at 130 °C for 4 hrs. 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 recrystallized from ethyl acetate.