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Acta Crystallogr Sect E Struct Rep Online. 2009 November 1; 65(Pt 11): o2714–o2715.
Published online 2009 October 10. doi:  10.1107/S1600536809040100
PMCID: PMC2971225

5-Methyl-3-[1-(2-pyridylmeth­yl)-1H-benzimidazol-2-ylmeth­yl]isoxazole

Abstract

The title compound, C18H16N4O, is built up from fused six- and five-membered rings linked to a five-membered isoxazole ring and to a six-membered pyridine ring through a CH2 group. The fused-ring system is essentially planar, with a maximum deviation of 0.019 (1) Å. It forms inter­planar angles of 70.03 (7)° with the isoxazole ring and 81.68 (7)° with the pyridine ring; the two latter rings are also planar, the maximum deviations from the mean planes being 0.0028 (15) and 0.0047 (12) Å, respectively. In the crystal, weak inter­molecular non-classical C—H(...)N hydrogen bonds link the mol­ecules, forming a zigzag-like chain parallel to the b axis. A weak intra­molecular C—H(...)N hydrogen bond may help to define the conformation of the mol­ecule.

Related literature

Isoxazoles and their derivatives are key inter­mediates for the preparation of products which mimics natural compounds, see: Baraldi et al. (1987 [triangle]). For their biological activity, see: Boros et al. (2006 [triangle]); Desai & Desai (2006 [triangle]); Eddington et al. (2002 [triangle]); Kang et al. (2000 [triangle]); Ko et al. (1998 [triangle]); Lee & Kim (2002 [triangle]); Sbai et al. (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2714-scheme1.jpg

Experimental

Crystal data

  • C18H16N4O
  • M r = 304.35
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2714-efi4.jpg
  • a = 11.0761 (2) Å
  • b = 8.6535 (1) Å
  • c = 16.5920 (3) Å
  • β = 103.136 (1)°
  • V = 1548.68 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 298 K
  • 0.28 × 0.16 × 0.06 mm

Data collection

  • Bruker X8 Kappa APEX II diffractometer
  • Absorption correction: none
  • 29777 measured reflections
  • 3567 independent reflections
  • 2460 reflections with I > 2σ(I)
  • R int = 0.047

Refinement

  • R[F 2 > 2σ(F 2)] = 0.040
  • wR(F 2) = 0.105
  • S = 1.01
  • 3567 reflections
  • 214 parameters
  • H-atom parameters constrained
  • Δρmax = 0.15 e Å−3
  • Δρmin = −0.14 e Å−3

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]) and PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809040100/dn2494sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809040100/dn2494Isup2.hkl

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

Acknowledgments

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.

supplementary crystallographic information

Comment

Isoxazoles and their derivatives are key intermediates for the preparation of products which mimics natural compounds (Baraldi et al., 1987). They have long been targeted in synthetic investigation for their known biological activities and pharmacological properties such as antiviral (Lee & Kim, 2002), anticonvulsant (Eddington et al., 2002), anti-inflammatory (Ko et al., 1998), and anti-bacterial activity (Kang et al., 2000). Also, varied pharmacological and chelating properties are associated with benzimidazole derivatives and pyridine (Sbai et al., 2003, Desai & Desai, 2006, Boros et al. 2006). Thus it is expected that the association of benzimidazole and pyridine moiety with the isoxazole system would affect significantly the biological and complexing properties.

The molecule is built up from fused six and five-membered rings linked together to a five-membered isoxazole ring and to six-membered pyridine ring through a CH2 chain (Fig. 1). The fused ring system is essentially planar, with maximum deviation of -0.008 (2) and -0.019 (1) Å for atoms C4 and C12 respectively. It forms interplanar angles of 70.03 (7)° with the isoxazole ring and 81.68 (7)°t with the pyridine ring. These two last rings are also planar with maximum deviation from the mean planes being 0.0028 (15) at C1 and 0.0047 (12) at N4 for the isoxazole and the pyridine ring respectively.

There is a a weak intermolecular non classical C—H···N hydrogen bond linking the molecules to form a chain parallel to the (Table 1, Fig. 1). Weak intramolecular hydrogen bonds C—H···N may be responsible for the conformation of the molecule (Fig. 1, Table 1).

Experimental

To a solution of 3-((1H-benzimidazol-2-yl)methyl)-5-methylisoxazole (0.85 g, 4 mmol) in DMF (20 ml) was added (0.60 g, 4.4 mmol) of K2CO3. The mixture was stirred for 10 min at rt, and then 2-(chloromethyl)pyridine hydrochloride (0.72 g, 4.4 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 24 h. whereupon a white solid was deposited. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was subjected to a column chromatography (silica gel, hexane/ethyl acetate, 7:3, v/v) to give 5-methyl-3-((1-(pyridin-2-ylmethyl)-1H-benzimidazol-2-yl)methyl)isoxazole as a white crystal in 65% yield (0.79 g).

Refinement

All H atoms were fixed geometrically and treated as riding with C—H = 0.96 Å (methyl), 0.97 Å (methylene) or 0.93 Å (aromatic) with Uiso(H) = 1.2Ueq(aromatic, methylene) or Uiso(H) = 1.5Ueq(methyl).

Figures

Fig. 1.
: Molecular view with the atom labeling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. H bonds are shown as dashed lines.
Fig. 2.
: Partial packing view showing the formation of a chain through C—H···N hydrogen bond shown as dashed lines. H atoms not involved in hydrogen bondings have been omitted for clarity. [Symmetry code: (i) 1/2 - x, y - 1/2, ...

Crystal data

C18H16N4OF(000) = 640
Mr = 304.35Dx = 1.305 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 3567 reflections
a = 11.0761 (2) Åθ = 2.5–27.5°
b = 8.6535 (1) ŵ = 0.09 mm1
c = 16.5920 (3) ÅT = 298 K
β = 103.136 (1)°Block, white
V = 1548.68 (4) Å30.28 × 0.16 × 0.06 mm
Z = 4

Data collection

Bruker X8 APEX Diffractometer2460 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.047
graphiteθmax = 27.5°, θmin = 2.5°
[var phi] and ω scansh = −14→14
29777 measured reflectionsk = −11→11
3567 independent reflectionsl = −21→17

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.105w = 1/[σ2(Fo2) + (0.0445P)2 + 0.2578P] where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max < 0.001
3567 reflectionsΔρmax = 0.15 e Å3
214 parametersΔρmin = −0.14 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0099 (13)

Special details

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
O10.35108 (10)−0.03671 (13)0.02360 (6)0.0584 (3)
N10.28238 (12)0.07631 (17)0.05503 (8)0.0587 (4)
N20.14275 (11)0.00694 (14)0.28340 (7)0.0462 (3)
N30.02122 (11)0.07134 (13)0.16088 (7)0.0421 (3)
N4−0.03858 (11)0.38647 (14)0.14258 (7)0.0472 (3)
C10.41164 (13)−0.12534 (17)0.08719 (9)0.0461 (4)
C20.38459 (14)−0.07581 (17)0.15741 (9)0.0467 (4)
H20.4130−0.11630.21020.056*
C30.30411 (13)0.05044 (16)0.13448 (9)0.0438 (3)
C40.24511 (14)0.15139 (17)0.18861 (9)0.0519 (4)
H4B0.30670.17740.23840.061 (5)*
H4A0.21780.24690.15950.067 (5)*
C50.13705 (13)0.07608 (15)0.21254 (8)0.0414 (3)
C60.02351 (13)−0.04756 (15)0.27876 (8)0.0428 (3)
C7−0.02328 (16)−0.13135 (18)0.33632 (10)0.0559 (4)
H70.0275−0.16080.38660.067*
C8−0.14703 (17)−0.1693 (2)0.31653 (11)0.0655 (5)
H8−0.1803−0.22490.35430.079*
C9−0.22337 (16)−0.1265 (2)0.24140 (11)0.0657 (5)
H9−0.3067−0.15380.23020.079*
C10−0.17938 (14)−0.04485 (19)0.18304 (10)0.0553 (4)
H10−0.2307−0.01650.13270.066*
C11−0.05416 (13)−0.00683 (15)0.20323 (8)0.0416 (3)
C12−0.01820 (15)0.13746 (17)0.07846 (8)0.0469 (4)
H12A−0.08120.07080.04580.052 (4)*
H12B0.05210.13750.05260.056 (4)*
C13−0.06934 (12)0.29955 (15)0.07513 (7)0.0380 (3)
C14−0.08168 (16)0.53187 (18)0.13659 (10)0.0568 (4)
H14−0.06190.59400.18350.068*
C15−0.15277 (16)0.5944 (2)0.06597 (11)0.0610 (4)
H15−0.18010.69610.06500.073*
C16−0.18271 (15)0.5037 (2)−0.00321 (10)0.0600 (4)
H16−0.23050.5428−0.05240.072*
C17−0.14106 (13)0.35385 (18)0.00120 (9)0.0496 (4)
H17−0.16080.2897−0.04490.060*
C180.48944 (16)−0.2503 (2)0.06534 (11)0.0633 (4)
H18A0.4381−0.32180.02860.095*
H18B0.5309−0.30330.11470.095*
H18C0.5499−0.20680.03860.095*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0632 (7)0.0749 (8)0.0368 (6)0.0062 (6)0.0106 (5)0.0119 (5)
N10.0609 (8)0.0670 (9)0.0474 (8)0.0091 (7)0.0107 (6)0.0143 (6)
N20.0487 (7)0.0438 (7)0.0433 (7)0.0026 (5)0.0050 (5)0.0042 (5)
N30.0491 (7)0.0372 (6)0.0381 (6)0.0050 (5)0.0062 (5)0.0019 (5)
N40.0572 (7)0.0463 (7)0.0355 (6)0.0096 (6)0.0050 (5)−0.0026 (5)
C10.0454 (8)0.0521 (9)0.0390 (8)−0.0074 (7)0.0056 (6)0.0096 (6)
C20.0527 (8)0.0491 (8)0.0355 (7)−0.0054 (7)0.0040 (6)0.0085 (6)
C30.0440 (8)0.0443 (8)0.0414 (8)−0.0110 (6)0.0059 (6)0.0065 (6)
C40.0578 (9)0.0440 (8)0.0526 (9)−0.0097 (7)0.0100 (7)−0.0012 (7)
C50.0484 (8)0.0321 (7)0.0420 (8)0.0014 (6)0.0068 (6)−0.0029 (6)
C60.0475 (8)0.0373 (7)0.0432 (8)0.0054 (6)0.0096 (6)−0.0002 (6)
C70.0647 (10)0.0542 (9)0.0504 (9)0.0019 (8)0.0161 (8)0.0061 (7)
C80.0718 (12)0.0661 (11)0.0664 (11)−0.0091 (9)0.0321 (9)−0.0011 (9)
C90.0516 (10)0.0804 (12)0.0689 (11)−0.0106 (9)0.0216 (9)−0.0147 (10)
C100.0481 (9)0.0634 (10)0.0520 (9)0.0048 (7)0.0063 (7)−0.0097 (8)
C110.0475 (8)0.0354 (7)0.0419 (8)0.0058 (6)0.0100 (6)−0.0044 (6)
C120.0575 (9)0.0478 (8)0.0337 (7)0.0062 (7)0.0068 (6)−0.0024 (6)
C130.0392 (7)0.0435 (8)0.0306 (7)0.0010 (6)0.0067 (5)0.0019 (6)
C140.0714 (11)0.0463 (9)0.0523 (9)0.0088 (8)0.0136 (8)−0.0049 (7)
C150.0641 (10)0.0475 (9)0.0717 (12)0.0137 (8)0.0164 (9)0.0134 (8)
C160.0548 (9)0.0641 (10)0.0551 (10)0.0061 (8)0.0001 (7)0.0237 (8)
C170.0514 (9)0.0563 (9)0.0365 (8)−0.0040 (7)0.0004 (6)0.0035 (7)
C180.0676 (11)0.0635 (10)0.0621 (10)0.0020 (8)0.0216 (9)0.0026 (8)

Geometric parameters (Å, °)

O1—C11.3526 (17)C7—H70.9300
O1—N11.4100 (17)C8—C91.388 (2)
N1—C31.3044 (17)C8—H80.9300
N2—C51.3079 (17)C9—C101.374 (2)
N2—C61.3880 (18)C9—H90.9300
N3—C51.3720 (17)C10—C111.390 (2)
N3—C111.3840 (18)C10—H100.9300
N3—C121.4548 (16)C12—C131.5090 (19)
N4—C131.3270 (16)C12—H12A0.9700
N4—C141.3414 (19)C12—H12B0.9700
C1—C21.338 (2)C13—C171.3833 (18)
C1—C181.478 (2)C14—C151.366 (2)
C2—C31.407 (2)C14—H140.9300
C2—H20.9300C15—C161.368 (2)
C3—C41.504 (2)C15—H150.9300
C4—C51.494 (2)C16—C171.372 (2)
C4—H4B0.9700C16—H160.9300
C4—H4A0.9700C17—H170.9300
C6—C71.390 (2)C18—H18A0.9600
C6—C111.3945 (19)C18—H18B0.9600
C7—C81.375 (2)C18—H18C0.9600
C1—O1—N1108.57 (11)C10—C9—H9119.0
C3—N1—O1105.28 (11)C8—C9—H9119.0
C5—N2—C6104.75 (11)C9—C10—C11116.48 (15)
C5—N3—C11106.49 (11)C9—C10—H10121.8
C5—N3—C12127.86 (12)C11—C10—H10121.8
C11—N3—C12125.63 (12)N3—C11—C10132.63 (13)
C13—N4—C14116.77 (12)N3—C11—C6105.05 (12)
C2—C1—O1109.15 (13)C10—C11—C6122.32 (14)
C2—C1—C18134.95 (14)N3—C12—C13115.46 (11)
O1—C1—C18115.90 (13)N3—C12—H12A108.4
C1—C2—C3105.48 (12)C13—C12—H12A108.4
C1—C2—H2127.3N3—C12—H12B108.4
C3—C2—H2127.3C13—C12—H12B108.4
N1—C3—C2111.51 (13)H12A—C12—H12B107.5
N1—C3—C4119.88 (13)N4—C13—C17122.74 (13)
C2—C3—C4128.61 (13)N4—C13—C12118.28 (11)
C5—C4—C3112.85 (12)C17—C13—C12118.90 (12)
C5—C4—H4B109.0N4—C14—C15124.12 (15)
C3—C4—H4B109.0N4—C14—H14117.9
C5—C4—H4A109.0C15—C14—H14117.9
C3—C4—H4A109.0C14—C15—C16118.38 (15)
H4B—C4—H4A107.8C14—C15—H15120.8
N2—C5—N3113.28 (12)C16—C15—H15120.8
N2—C5—C4124.10 (13)C15—C16—C17118.87 (14)
N3—C5—C4122.62 (12)C15—C16—H16120.6
N2—C6—C7129.63 (13)C17—C16—H16120.6
N2—C6—C11110.42 (12)C16—C17—C13119.12 (14)
C7—C6—C11119.95 (14)C16—C17—H17120.4
C8—C7—C6117.89 (15)C13—C17—H17120.4
C8—C7—H7121.1C1—C18—H18A109.5
C6—C7—H7121.1C1—C18—H18B109.5
C7—C8—C9121.43 (16)H18A—C18—H18B109.5
C7—C8—H8119.3C1—C18—H18C109.5
C9—C8—H8119.3H18A—C18—H18C109.5
C10—C9—C8121.93 (16)H18B—C18—H18C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2···N4i0.932.523.385 (2)155
C12—H12B···N10.972.603.479 (2)151

Symmetry codes: (i) −x+1/2, y−1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DN2494).

References

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