PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2012 June 1; 68(Pt 6): o1683.
Published online 2012 May 12. doi:  10.1107/S1600536812019897
PMCID: PMC3379279

Ethyl 2-(4-bromo­phen­yl)-1-phenyl-1H-benzimidazole-5-carboxyl­ate

Abstract

In the title compound, C22H17BrN2O2, the benzimidazole ring system is essentially planar, with a maximum deviation of 0.017 (1) Å, and forms dihedral angles of 27.79 (6) and 64.43 (6)° with the phenyl and bromo-substituted benzene rings, respectively. In the crystal, mol­ecules are linked into one-dimensional chains along the a axis by weak C—H(...)O hydrogen bonds. Weak inter­molecular C—H(...)π inter­actions are also present.

Related literature  

For background to and the biological activities of benzimidazoles, see: Townsend & Revankar (1970 [triangle]); Rao et al. (2002 [triangle]); Thakurdesai et al. (2007 [triangle]); Dubey & Sanyal (2010 [triangle]); Lacey (1990 [triangle]). For a related structure, see: Arumugam et al. (2010 [triangle]). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-68-o1683-scheme1.jpg

Experimental  

Crystal data  

  • C22H17BrN2O2
  • M r = 421.29
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-68-o1683-efi1.jpg
  • a = 9.3121 (2) Å
  • b = 9.8136 (2) Å
  • c = 11.8458 (2) Å
  • α = 108.217 (1)°
  • β = 101.135 (1)°
  • γ = 109.361 (1)°
  • V = 915.39 (3) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 2.27 mm−1
  • T = 100 K
  • 0.42 × 0.33 × 0.15 mm

Data collection  

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.450, T max = 0.728
  • 21718 measured reflections
  • 5326 independent reflections
  • 4846 reflections with I > 2σ(I)
  • R int = 0.025

Refinement  

  • R[F 2 > 2σ(F 2)] = 0.027
  • wR(F 2) = 0.071
  • S = 1.06
  • 5326 reflections
  • 245 parameters
  • H-atom parameters constrained
  • Δρmax = 0.53 e Å−3
  • Δρmin = −0.65 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812019897/lh5466sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812019897/lh5466Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812019897/lh5466Isup3.cml

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

Acknowledgments

The authors thank the Malaysian Government and Universiti Sains Malaysia for the Research University grants Nos. 1001/PFIZIK/811151 and 1001/PSK/8620012. The authors also thank Pharmacogenetic and Novel Therapeutic Research, Institute for Research in Mol­ecular Medicine, Universiti Sains Malaysia.

supplementary crystallographic information

Comment

Benzimidazoles are a class of bioactive heterocyclic compounds which exhibit a wide range of activities such as anti-cancer (Townsend & Revankar, 1970), anti-HIV (Rao et al., 2002), anti-inflammatory (Thakurdesai et al., 2007) and anthelmintics (Dubey & Sanyal, 2010). The primary mechanism of action of benzimidazoles as anthelmintics is by binding to free β-tubulin and inhibiting its polymerization (Lacey, 1990). A number of benzimidazoles have been shown to also inhibit mammalian tubulin polymerization and to be aneugenic in vivo.

The molecular structure is shown in Fig. 1. Bond lengths and angles are within normal ranges and are comparable to a related structure (Arumugam et al.,2010). The benzimidazole ring system (N1/N2/C1—C7) is essentially planar with a maximum deviation of 0.017 (1) Å for atom C7. The dihedral angles of the benzimidazole ring (N1/N2/C1—C7) with the phenyl ring (C14–C19) and the bromo-substituted benzene ring (C8–C13) are 27.79 (6) and 64.43 (6)°, respectively.

In the crystal packing (Fig. 2), intermolecular C15—H15A···O2i (Table 1) hydrogen bonds link the molecules into one-dimensional zigzag chains along the a-axis. In addition, the crystal structure is further stabilized by the intermolecular C21—H21A···Cg1iii and C19—H19A···Cg2ii (Table 1) interactions (Cg1 and Cg2 are the centroids of N1/N1/C1/C6/C7 and C8–C13 rings, respectively).

Experimental

Ethyl 3-amino-4-(phenyl amino) benzoate (0.84 mmol) and sodium metabisulfite adduct of bromo benzaldehyde (1.68 mmol) were dissolved in DMF. The reaction mixture was reflux at 403K for 2 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 recrystallized from ethyl acetate.

Refinement

All H atoms were positioned geometrically [C–H = 0.95–0.99 Å] and refined using a riding model with Uiso(H) = 1.2 and 1.5 Ueq(C). A rotating group model was applied to the methyl group.

Figures

Fig. 1.
The molecular structure of the title compound, showing 30% probability displacement ellipsoids.
Fig. 2.
The crystal packing of the title compound. The H atoms not involved in the intermolecular interactions (dashed lines) have been omitted for clarity.

Crystal data

C22H17BrN2O2Z = 2
Mr = 421.29F(000) = 428
Triclinic, P1Dx = 1.528 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.3121 (2) ÅCell parameters from 9874 reflections
b = 9.8136 (2) Åθ = 2.4–32.7°
c = 11.8458 (2) ŵ = 2.27 mm1
α = 108.217 (1)°T = 100 K
β = 101.135 (1)°Block, colourless
γ = 109.361 (1)°0.42 × 0.33 × 0.15 mm
V = 915.39 (3) Å3

Data collection

Bruker SMART APEXII CCD area-detector diffractometer5326 independent reflections
Radiation source: fine-focus sealed tube4846 reflections with I > I > 2σ(I)
Graphite monochromatorRint = 0.025
[var phi] and ω scansθmax = 30.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −13→13
Tmin = 0.450, Tmax = 0.728k = −13→13
21718 measured reflectionsl = −16→16

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.027Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.071H-atom parameters constrained
S = 1.06w = 1/[σ2(Fo2) + (0.0366P)2 + 0.3723P] where P = (Fo2 + 2Fc2)/3
5326 reflections(Δ/σ)max = 0.001
245 parametersΔρmax = 0.53 e Å3
0 restraintsΔρmin = −0.65 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
Br1−0.680059 (17)−0.321236 (17)−0.071893 (14)0.02360 (5)
O10.66395 (12)−0.10601 (12)0.40079 (10)0.0201 (2)
O20.84619 (13)0.14498 (13)0.46778 (10)0.0230 (2)
N10.12223 (14)−0.10878 (14)0.20976 (11)0.0180 (2)
N20.16438 (14)0.14058 (14)0.23396 (11)0.0163 (2)
C10.31426 (17)0.14481 (16)0.28300 (13)0.0167 (2)
C20.46861 (18)0.26876 (17)0.34068 (14)0.0202 (3)
H2A0.48670.37360.35050.024*
C30.59380 (18)0.23123 (17)0.38280 (14)0.0205 (3)
H3A0.70050.31230.42260.025*
C40.56651 (17)0.07511 (17)0.36785 (13)0.0181 (3)
C50.41259 (17)−0.04732 (17)0.30997 (13)0.0184 (3)
H5A0.3946−0.15220.29970.022*
C60.28543 (17)−0.01088 (16)0.26745 (13)0.0168 (2)
C70.05354 (17)−0.01604 (16)0.19171 (12)0.0160 (2)
C8−0.12145 (16)−0.07748 (16)0.13144 (12)0.0164 (2)
C9−0.21833 (17)−0.21394 (17)0.14191 (13)0.0182 (3)
H9A−0.1695−0.25910.18890.022*
C10−0.38444 (17)−0.28386 (17)0.08468 (13)0.0192 (3)
H10A−0.4497−0.37410.09450.023*
C11−0.45403 (17)−0.21985 (17)0.01266 (13)0.0183 (3)
C12−0.36095 (17)−0.08657 (17)−0.00143 (13)0.0183 (3)
H12A−0.4102−0.0453−0.05200.022*
C13−0.19447 (17)−0.01399 (16)0.05949 (13)0.0172 (2)
H13A−0.13030.07880.05220.021*
C140.13582 (17)0.27765 (16)0.24107 (13)0.0168 (2)
C150.04564 (17)0.32281 (17)0.31392 (13)0.0187 (3)
H15A0.00000.26190.35690.022*
C160.02336 (18)0.45862 (18)0.32284 (14)0.0220 (3)
H16A−0.03690.49140.37320.026*
C170.08845 (19)0.54698 (18)0.25870 (15)0.0236 (3)
H17A0.07290.63970.26540.028*
C180.1760 (2)0.49909 (18)0.18500 (15)0.0250 (3)
H18A0.21880.55820.14000.030*
C190.20176 (19)0.36444 (17)0.17651 (14)0.0208 (3)
H19A0.26350.33260.12730.025*
C200.70792 (17)0.04581 (17)0.41792 (13)0.0183 (3)
C210.79333 (17)−0.14750 (17)0.44476 (13)0.0199 (3)
H21A0.8430−0.09220.53750.024*
H21B0.8778−0.11790.40630.024*
C220.7174 (2)−0.32313 (19)0.40531 (15)0.0264 (3)
H22A0.8004−0.35800.43160.040*
H22B0.6670−0.37580.31350.040*
H22C0.6353−0.35020.44510.040*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Br10.01607 (8)0.02227 (8)0.02755 (8)0.00650 (6)0.00244 (6)0.00860 (6)
O10.0153 (5)0.0192 (5)0.0243 (5)0.0073 (4)0.0042 (4)0.0083 (4)
O20.0168 (5)0.0232 (5)0.0259 (5)0.0062 (4)0.0054 (4)0.0095 (4)
N10.0162 (5)0.0167 (5)0.0189 (5)0.0060 (4)0.0031 (4)0.0071 (5)
N20.0162 (5)0.0144 (5)0.0182 (5)0.0060 (4)0.0053 (4)0.0071 (4)
C10.0171 (6)0.0170 (6)0.0176 (6)0.0076 (5)0.0063 (5)0.0082 (5)
C20.0196 (7)0.0163 (6)0.0232 (7)0.0057 (5)0.0067 (5)0.0083 (5)
C30.0167 (6)0.0182 (6)0.0235 (7)0.0042 (5)0.0061 (5)0.0082 (5)
C40.0167 (6)0.0190 (6)0.0182 (6)0.0073 (5)0.0059 (5)0.0075 (5)
C50.0183 (6)0.0171 (6)0.0193 (6)0.0071 (5)0.0059 (5)0.0073 (5)
C60.0166 (6)0.0155 (6)0.0160 (6)0.0052 (5)0.0042 (5)0.0060 (5)
C70.0173 (6)0.0148 (6)0.0147 (6)0.0057 (5)0.0047 (5)0.0061 (5)
C80.0158 (6)0.0168 (6)0.0141 (6)0.0063 (5)0.0039 (5)0.0046 (5)
C90.0195 (6)0.0185 (6)0.0158 (6)0.0077 (5)0.0044 (5)0.0071 (5)
C100.0191 (6)0.0179 (6)0.0175 (6)0.0053 (5)0.0052 (5)0.0063 (5)
C110.0164 (6)0.0193 (6)0.0170 (6)0.0077 (5)0.0049 (5)0.0049 (5)
C120.0207 (7)0.0188 (6)0.0166 (6)0.0111 (5)0.0053 (5)0.0062 (5)
C130.0188 (6)0.0164 (6)0.0166 (6)0.0077 (5)0.0064 (5)0.0064 (5)
C140.0171 (6)0.0151 (6)0.0163 (6)0.0061 (5)0.0035 (5)0.0058 (5)
C150.0176 (6)0.0197 (6)0.0184 (6)0.0075 (5)0.0055 (5)0.0079 (5)
C160.0202 (7)0.0218 (7)0.0230 (7)0.0107 (6)0.0062 (5)0.0064 (6)
C170.0234 (7)0.0170 (6)0.0267 (7)0.0084 (6)0.0027 (6)0.0076 (6)
C180.0322 (8)0.0193 (7)0.0236 (7)0.0087 (6)0.0086 (6)0.0117 (6)
C190.0262 (7)0.0179 (6)0.0190 (6)0.0087 (6)0.0100 (6)0.0075 (5)
C200.0183 (6)0.0200 (6)0.0172 (6)0.0080 (5)0.0074 (5)0.0076 (5)
C210.0178 (6)0.0230 (7)0.0187 (6)0.0105 (6)0.0043 (5)0.0075 (5)
C220.0304 (8)0.0243 (7)0.0254 (7)0.0135 (6)0.0076 (6)0.0100 (6)

Geometric parameters (Å, º)

Br1—C111.8967 (14)C10—C111.391 (2)
O1—C201.3428 (17)C10—H10A0.9500
O1—C211.4506 (17)C11—C121.390 (2)
O2—C201.2124 (18)C12—C131.3949 (19)
N1—C71.3182 (17)C12—H12A0.9500
N1—C61.3856 (18)C13—H13A0.9500
N2—C11.3858 (17)C14—C191.3889 (19)
N2—C71.3950 (17)C14—C151.3906 (19)
N2—C141.4360 (17)C15—C161.391 (2)
C1—C21.398 (2)C15—H15A0.9500
C1—C61.4047 (19)C16—C171.392 (2)
C2—C31.385 (2)C16—H16A0.9500
C2—H2A0.9500C17—C181.386 (2)
C3—C41.414 (2)C17—H17A0.9500
C3—H3A0.9500C18—C191.396 (2)
C4—C51.3898 (19)C18—H18A0.9500
C4—C201.4915 (19)C19—H19A0.9500
C5—C61.3953 (19)C21—C221.500 (2)
C5—H5A0.9500C21—H21A0.9900
C7—C81.4692 (19)C21—H21B0.9900
C8—C131.4022 (19)C22—H22A0.9800
C8—C91.4031 (19)C22—H22B0.9800
C9—C101.387 (2)C22—H22C0.9800
C9—H9A0.9500
C20—O1—C21115.96 (11)C11—C12—H12A120.3
C7—N1—C6105.29 (11)C13—C12—H12A120.3
C1—N2—C7106.01 (11)C12—C13—C8120.27 (13)
C1—N2—C14124.37 (11)C12—C13—H13A119.9
C7—N2—C14129.28 (12)C8—C13—H13A119.9
N2—C1—C2131.97 (13)C19—C14—C15121.23 (13)
N2—C1—C6105.65 (12)C19—C14—N2119.07 (12)
C2—C1—C6122.36 (13)C15—C14—N2119.69 (12)
C3—C2—C1116.72 (13)C14—C15—C16118.92 (13)
C3—C2—H2A121.6C14—C15—H15A120.5
C1—C2—H2A121.6C16—C15—H15A120.5
C2—C3—C4121.52 (13)C15—C16—C17120.63 (14)
C2—C3—H3A119.2C15—C16—H16A119.7
C4—C3—H3A119.2C17—C16—H16A119.7
C5—C4—C3121.27 (13)C18—C17—C16119.74 (14)
C5—C4—C20120.79 (13)C18—C17—H17A120.1
C3—C4—C20117.94 (13)C16—C17—H17A120.1
C4—C5—C6117.74 (13)C17—C18—C19120.41 (14)
C4—C5—H5A121.1C17—C18—H18A119.8
C6—C5—H5A121.1C19—C18—H18A119.8
N1—C6—C5129.29 (13)C14—C19—C18119.06 (13)
N1—C6—C1110.30 (12)C14—C19—H19A120.5
C5—C6—C1120.40 (13)C18—C19—H19A120.5
N1—C7—N2112.74 (12)O2—C20—O1123.35 (13)
N1—C7—C8121.69 (12)O2—C20—C4125.07 (13)
N2—C7—C8125.56 (12)O1—C20—C4111.58 (12)
C13—C8—C9119.05 (13)O1—C21—C22106.03 (12)
C13—C8—C7124.21 (12)O1—C21—H21A110.5
C9—C8—C7116.64 (12)C22—C21—H21A110.5
C10—C9—C8120.93 (13)O1—C21—H21B110.5
C10—C9—H9A119.5C22—C21—H21B110.5
C8—C9—H9A119.5H21A—C21—H21B108.7
C9—C10—C11119.00 (13)C21—C22—H22A109.5
C9—C10—H10A120.5C21—C22—H22B109.5
C11—C10—H10A120.5H22A—C22—H22B109.5
C12—C11—C10121.39 (13)C21—C22—H22C109.5
C12—C11—Br1119.62 (11)H22A—C22—H22C109.5
C10—C11—Br1118.97 (11)H22B—C22—H22C109.5
C11—C12—C13119.32 (13)
C7—N2—C1—C2−178.43 (15)C13—C8—C9—C10−1.5 (2)
C14—N2—C1—C2−4.5 (2)C7—C8—C9—C10−177.86 (12)
C7—N2—C1—C60.05 (14)C8—C9—C10—C112.2 (2)
C14—N2—C1—C6173.96 (12)C9—C10—C11—C12−0.9 (2)
N2—C1—C2—C3178.10 (14)C9—C10—C11—Br1177.12 (10)
C6—C1—C2—C3−0.2 (2)C10—C11—C12—C13−1.0 (2)
C1—C2—C3—C40.1 (2)Br1—C11—C12—C13−179.04 (10)
C2—C3—C4—C50.1 (2)C11—C12—C13—C81.7 (2)
C2—C3—C4—C20−179.00 (13)C9—C8—C13—C12−0.5 (2)
C3—C4—C5—C6−0.3 (2)C7—C8—C13—C12175.61 (13)
C20—C4—C5—C6178.81 (12)C1—N2—C14—C1965.95 (18)
C7—N1—C6—C5178.30 (14)C7—N2—C14—C19−121.62 (16)
C7—N1—C6—C1−0.54 (15)C1—N2—C14—C15−112.87 (15)
C4—C5—C6—N1−178.52 (13)C7—N2—C14—C1559.56 (19)
C4—C5—C6—C10.2 (2)C19—C14—C15—C16−0.8 (2)
N2—C1—C6—N10.30 (15)N2—C14—C15—C16178.04 (13)
C2—C1—C6—N1178.95 (13)C14—C15—C16—C170.8 (2)
N2—C1—C6—C5−178.66 (12)C15—C16—C17—C180.1 (2)
C2—C1—C6—C50.0 (2)C16—C17—C18—C19−1.1 (2)
C6—N1—C7—N20.58 (15)C15—C14—C19—C18−0.2 (2)
C6—N1—C7—C8179.77 (12)N2—C14—C19—C18−179.03 (13)
C1—N2—C7—N1−0.40 (15)C17—C18—C19—C141.2 (2)
C14—N2—C7—N1−173.91 (13)C21—O1—C20—O2−0.62 (19)
C1—N2—C7—C8−179.56 (12)C21—O1—C20—C4179.17 (11)
C14—N2—C7—C86.9 (2)C5—C4—C20—O2178.78 (14)
N1—C7—C8—C13−149.98 (14)C3—C4—C20—O2−2.1 (2)
N2—C7—C8—C1329.1 (2)C5—C4—C20—O1−1.01 (18)
N1—C7—C8—C926.20 (19)C3—C4—C20—O1178.09 (12)
N2—C7—C8—C9−154.71 (13)C20—O1—C21—C22−175.08 (12)

Hydrogen-bond geometry (Å, º)

Cg1 and Cg2 are the centroids of the N1/N1/C1/C6/C7 and C8–C13 rings, respectively.

D—H···AD—HH···AD···AD—H···A
C15—H15A···O2i0.952.383.311 (2)166
C19—H19A···Cg2ii0.952.593.4534 (18)152
C21—H21A···Cg1iii0.992.643.5288 (15)149

Symmetry codes: (i) x−1, y, z; (ii) −x, −y, −z; (iii) −x+1, −y, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH5466).

References

  • Arumugam, N., Abdul Rahim, A. S., Osman, H., Quah, C. K. & Fun, H.-K. (2010). Acta Cryst. E66, o2412–o2413. [PMC free article] [PubMed]
  • Bruker (2009). SADABS, APEX2 and SAINTBruker AXS Inc., Madison, Wisconsin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.
  • Dubey, A. K. & Sanyal, P. K. (2010). Vet Scan, 5, 63.
  • Lacey, E. (1990). Parasitol. Today, 6, 112–115. [PubMed]
  • Rao, A., Chimirri, A., Clercq, E. D., Monforte, A. M., Monforte, P., Pannecouque, C. & Zappala, M. (2002). Il Farmaco, 57, 819–823. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Thakurdesai, P. A., Wadodkar, S. G. & Chopade, C. T. (2007). Pharmacologyonline, 1, 314–329.
  • Townsend, L. B. & Revankar, G. R. (1970). Chem. Rev. 70, 389–438. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography