PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 July 1; 66(Pt 7): o1678.
Published online 2010 June 16. doi:  10.1107/S1600536810018568
PMCID: PMC3007039

5-Meth­oxy-1-(3,4,5-trimethoxy­phen­yl)-1H-indole

Abstract

The title compound, C18H19NO4, was prepared as an indole derivative with possible anti­mitotic properties. The planes of the indole and trimethoxy­phenyl rings make a dihedral angle of 45.35 (5)° with one another. In the crystal, mol­ecules related by a twofold screw axis exhibit arene C—H(...)arene-π inter­actions which are 3.035 (1) Å in length.

Related literature

For a related structure, see: Suthar et al. (2005 [triangle]). For pharmaceutical applications of indoles, see: Fuwa & Sasaki (2009 [triangle]); Li & Martins (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o1678-scheme1.jpg

Experimental

Crystal data

  • C18H19NO4
  • M r = 313.34
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1678-efi1.jpg
  • a = 19.0036 (16) Å
  • b = 7.3179 (14) Å
  • c = 23.672 (4) Å
  • β = 96.802 (10)°
  • V = 3268.8 (9) Å3
  • Z = 8
  • Cu Kα radiation
  • μ = 0.74 mm−1
  • T = 295 K
  • 0.32 × 0.27 × 0.26 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • 6084 measured reflections
  • 2951 independent reflections
  • 2074 reflections with I > 2σ(I)
  • R int = 0.026
  • 3 standard reflections every 190 reflections intensity decay: 4%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037
  • wR(F 2) = 0.110
  • S = 1.00
  • 2951 reflections
  • 209 parameters
  • H-atom parameters constrained
  • Δρmax = 0.16 e Å−3
  • Δρmin = −0.16 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); 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]), Mercury (Macrae et al., 2006 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810018568/fl2291sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810018568/fl2291Isup2.hkl

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

Acknowledgments

This work was supported in part by funds provided by the University of North Carolina at Charlotte.

supplementary crystallographic information

Comment

The indole core is a common structure observed in a wide variety of biologically active compounds and pharmaceutical products (Li & Martins, 2003). Indole structures are considered as privileged structure motifs, due to their ability to bind many receptors within the body (Fuwa & Sasaki, 2009). As a result, there has been a great deal of research dedicated to incorporating the indole functionality in the design and synthesis of novel anti-mitotic compounds for the treatment of cancer. The title compound was prepared as an indole derivative with possible anti-mitotic properties.

The structure of the title compound is shown in Fig. 1. The plane of the indole ring and the plane of the trimethoxyphenyl ring make a 45.35 (5)° angle with one another. The deviation of methoxy carbon C19 from the indole mean plane is 0.050 (3) Å. The deviations of methoxy carbons C16, C17, and C18 from the plane of the phenyl ring are 0.065 (3) Å, 1.157 (3) Å, and 0.138 (3) Å, respectively. Molecules related by a two-fold screw axis exhibit arene C—H··· arene π interactions, as shown in Fig. 2. The interaction is between C4—H of one molecule and the six membered (C4 through C9) aromatic ring of the screw-related molecule. The H··· ring-centroid distance is 3.035 (1) Å, and the H··· ring-centroid line makes an angle of 5.6 (3)° with the normal to the plane of the ring.

In a comparable structure, 1-(3,4,5-Trimethoxyphenyl)naphthalene (Suthar et al., 2005), the angle between the planes of the napthylene ring and the trimethoxyphenyl ring is 68.19 (10)°.

Experimental

Preparation of the title compound (III) (See Synthesis scheme): To a Schlenk flask equipped with a magnetic stir bar, 1.47 g (10 mmol) of 5-methoxyindole (II), 6.36 g (30 mmol) of K3PO4, and 0.190 g (10 mol %) of CuI were added. The reaction flask was then purged with nitrogen gas and charged with 2.94 g (10 mmol) of 5-iodo-1,2,3-trimethoxybenzene (I), 0.22 ml (20 mol %) of N,N'-dimethylethylenediamine, and 25.0 ml of dry degassed toluene. The reaction mixture was heated to reflux for 24 hours. Upon completion, the crude reaction mixture was filtered through a celite plug, and concentrated on a rotary evaporator to yield an off-white solid. The solid was recrystallized from ethanol to obtain the x-ray quality crystals. Pure product was obtained in 86 % yield (2.70 g). Melting point: 99-101°C. MS(E1): M+ 313 m/z, 298 m/z. 1H NMR (300 MHz, DMSO-d) δ7.62 (d, 1H), 7.56 (d,1H), 7.14 (d,1H), 6.84(d,1H), 6.82 (s, 2H), 6.58 (d, 1H), 3.85 (s,6H), 3.78 (s, 3H), 3.71 (s,3H)

Refinement

All H atoms were constrained using a riding model. The aromatic C—H bond lengths were fixed at 0.93 Å, with Uiso(H) = 1.2 Ueq(C). The methyl C—H bond lengths were fixed at 0.96 Å, with Uiso(H) = 1.5 Ueq(C). An idealized tetrahedral geometry was used for the methyl groups, and the torsion angles around the O—C bonds were refined.

Figures

Fig. 1.
View of the title compound (50% probability displacement ellipsoids)
Fig. 2.
Packing diagram showing the arene C—H···π interactions between molecules related by a two-fold screw axis
Fig. 3.
Synthesis scheme

Crystal data

C18H19NO4F(000) = 1328
Mr = 313.34Dx = 1.273 Mg m3
Monoclinic, C2/cCu Kα radiation, λ = 1.54184 Å
Hall symbol: -C 2ycCell parameters from 24 reflections
a = 19.0036 (16) Åθ = 6.4–20.8°
b = 7.3179 (14) ŵ = 0.74 mm1
c = 23.672 (4) ÅT = 295 K
β = 96.802 (10)°Prism, colorless
V = 3268.8 (9) Å30.32 × 0.27 × 0.26 mm
Z = 8

Data collection

Enraf–Nonius CAD-4 diffractometerθmax = 67.4°, θmin = 3.8°
non–profiled ω/2θ scansh = −22→22
6084 measured reflectionsk = −8→0
2951 independent reflectionsl = −28→28
2074 reflections with I > 2σ(I)3 standard reflections every 190 reflections
Rint = 0.026 intensity decay: 4%

Refinement

Refinement on F2H-atom parameters constrained
Least-squares matrix: fullw = 1/[σ2(Fo2) + (0.0613P)2 + 0.605P] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.037(Δ/σ)max < 0.001
wR(F2) = 0.110Δρmax = 0.16 e Å3
S = 1.00Δρmin = −0.16 e Å3
2951 reflectionsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
209 parametersExtinction coefficient: 0.00188 (13)
0 restraints

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

xyzUiso*/Ueq
O140.15356 (6)0.12928 (15)0.49143 (5)0.0511 (3)
O130.07247 (7)0.29172 (17)0.40657 (5)0.0575 (3)
O50.40130 (7)0.77324 (19)0.74372 (5)0.0647 (4)
N0.14855 (7)0.67340 (19)0.60827 (5)0.0451 (3)
O120.02905 (7)0.64188 (17)0.41594 (5)0.0562 (4)
C110.08846 (8)0.6630 (2)0.51210 (7)0.0459 (4)
H150.07410.78340.51590.055*
C150.15105 (8)0.3970 (2)0.55189 (6)0.0429 (4)
H110.17730.33910.58240.051*
C140.13334 (8)0.3050 (2)0.50087 (7)0.0414 (4)
C80.21611 (9)0.6831 (2)0.63793 (6)0.0428 (4)
C70.27934 (9)0.6005 (2)0.62755 (7)0.0488 (4)
H40.28130.52350.59650.059*
C130.09214 (8)0.3894 (2)0.45562 (6)0.0430 (4)
C120.06941 (8)0.5691 (2)0.46185 (7)0.0435 (4)
C100.12910 (8)0.5758 (2)0.55666 (6)0.0427 (4)
C60.33859 (10)0.6368 (3)0.66472 (7)0.0519 (4)
H30.38130.58230.65890.062*
C50.33640 (10)0.7540 (2)0.71127 (7)0.0496 (4)
C30.14176 (10)0.8679 (2)0.68041 (7)0.0539 (5)
H90.1240.950.70520.065*
C180.20053 (9)0.0443 (2)0.53514 (7)0.0532 (4)
H18A0.2109−0.07770.52370.08*
H18B0.17860.040.56960.08*
H18C0.24370.11340.54150.08*
C40.27495 (10)0.8393 (2)0.72137 (7)0.0520 (4)
H70.2740.91790.75210.062*
C20.10450 (10)0.7872 (2)0.63464 (7)0.0512 (4)
H80.05660.80570.62280.061*
C90.21305 (9)0.8044 (2)0.68373 (7)0.0466 (4)
C160.00926 (10)0.8294 (3)0.41920 (8)0.0597 (5)
H16A−0.01870.86440.38440.09*
H16B0.05110.90380.42480.09*
H16C−0.01790.84610.45050.09*
C170.10615 (13)0.3480 (3)0.35877 (8)0.0751 (6)
H17A0.08950.27390.32650.113*
H17B0.15650.33420.36730.113*
H17C0.09510.47380.35040.113*
C190.40555 (13)0.8959 (3)0.78968 (9)0.0857 (7)
H1A0.45310.89730.80860.129*
H1B0.37360.8580.81590.129*
H1C0.39291.01620.77590.129*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O140.0641 (7)0.0342 (6)0.0528 (7)0.0029 (5)−0.0026 (6)−0.0024 (5)
O130.0760 (8)0.0458 (7)0.0466 (6)−0.0098 (6)−0.0091 (6)−0.0038 (5)
O50.0659 (8)0.0628 (9)0.0605 (8)−0.0043 (7)−0.0125 (6)−0.0102 (7)
N0.0516 (8)0.0402 (8)0.0423 (7)0.0020 (6)0.0006 (6)−0.0044 (6)
O120.0620 (8)0.0452 (7)0.0560 (7)0.0041 (6)−0.0155 (6)0.0022 (6)
C110.0497 (9)0.0362 (9)0.0503 (9)0.0013 (7)0.0003 (7)−0.0013 (7)
C150.0465 (9)0.0387 (9)0.0420 (8)−0.0023 (7)−0.0006 (7)0.0026 (7)
C140.0443 (8)0.0322 (8)0.0475 (8)−0.0049 (7)0.0050 (7)0.0006 (7)
C80.0522 (9)0.0359 (9)0.0394 (8)−0.0001 (7)0.0009 (7)−0.0006 (7)
C70.0568 (10)0.0445 (10)0.0446 (8)0.0004 (8)0.0043 (7)−0.0065 (7)
C130.0468 (9)0.0386 (9)0.0421 (8)−0.0093 (7)−0.0016 (7)−0.0018 (7)
C120.0409 (8)0.0398 (9)0.0480 (9)−0.0034 (7)−0.0027 (7)0.0044 (7)
C100.0458 (8)0.0383 (9)0.0431 (8)−0.0040 (7)0.0021 (7)−0.0025 (7)
C60.0531 (10)0.0494 (10)0.0528 (10)0.0010 (8)0.0044 (8)−0.0033 (8)
C50.0589 (10)0.0424 (10)0.0452 (9)−0.0040 (8)−0.0040 (8)0.0020 (7)
C30.0648 (11)0.0459 (10)0.0505 (9)0.0095 (8)0.0050 (8)−0.0088 (8)
C180.0551 (10)0.0418 (10)0.0619 (10)0.0023 (8)0.0034 (8)0.0063 (8)
C40.0704 (12)0.0417 (10)0.0423 (8)−0.0013 (9)−0.0001 (8)−0.0072 (7)
C20.0560 (10)0.0448 (9)0.0523 (9)0.0092 (8)0.0044 (8)−0.0017 (8)
C90.0608 (10)0.0371 (9)0.0409 (8)0.0014 (8)0.0022 (7)−0.0016 (7)
C160.0653 (12)0.0456 (11)0.0654 (12)0.0073 (9)−0.0046 (9)0.0097 (9)
C170.1107 (18)0.0663 (14)0.0487 (10)0.0058 (13)0.0109 (11)−0.0032 (10)
C190.0995 (17)0.0828 (17)0.0663 (13)0.0018 (14)−0.0254 (12)−0.0217 (12)

Geometric parameters (Å, °)

O14—C141.368 (2)C13—C121.397 (2)
O14—C181.427 (2)C6—C51.401 (2)
O13—C131.3769 (18)C6—H30.93
O13—C171.425 (2)C5—C41.370 (2)
O5—C51.381 (2)C3—C21.357 (2)
O5—C191.405 (2)C3—C91.426 (2)
N—C21.381 (2)C3—H90.93
N—C81.390 (2)C18—H18A0.96
N—C101.4255 (19)C18—H18B0.96
O12—C121.3622 (18)C18—H18C0.96
O12—C161.427 (2)C4—C91.412 (2)
C11—C121.384 (2)C4—H70.93
C11—C101.387 (2)C2—H80.93
C11—H150.93C16—H16A0.96
C15—C101.382 (2)C16—H16B0.96
C15—C141.389 (2)C16—H16C0.96
C15—H110.93C17—H17A0.96
C14—C131.394 (2)C17—H17B0.96
C8—C71.393 (2)C17—H17C0.96
C8—C91.408 (2)C19—H1A0.96
C7—C61.371 (2)C19—H1B0.96
C7—H40.93C19—H1C0.96
C14—O14—C18117.06 (12)C2—C3—C9107.72 (15)
C13—O13—C17114.63 (14)C2—C3—H9126.1
C5—O5—C19117.49 (16)C9—C3—H9126.1
C2—N—C8108.29 (13)O14—C18—H18A109.5
C2—N—C10125.44 (14)O14—C18—H18B109.5
C8—N—C10126.06 (14)H18A—C18—H18B109.5
C12—O12—C16117.38 (13)O14—C18—H18C109.5
C12—C11—C10119.38 (15)H18A—C18—H18C109.5
C12—C11—H15120.3H18B—C18—H18C109.5
C10—C11—H15120.3C5—C4—C9118.11 (15)
C10—C15—C14119.05 (15)C5—C4—H7120.9
C10—C15—H11120.5C9—C4—H7120.9
C14—C15—H11120.5C3—C2—N109.65 (16)
O14—C14—C15123.64 (14)C3—C2—H8125.2
O14—C14—C13115.72 (14)N—C2—H8125.2
C15—C14—C13120.63 (15)C8—C9—C4119.51 (16)
N—C8—C7130.78 (15)C8—C9—C3106.80 (15)
N—C8—C9107.54 (14)C4—C9—C3133.69 (16)
C7—C8—C9121.66 (15)O12—C16—H16A109.5
C6—C7—C8117.58 (16)O12—C16—H16B109.5
C6—C7—H4121.2H16A—C16—H16B109.5
C8—C7—H4121.2O12—C16—H16C109.5
O13—C13—C14119.30 (15)H16A—C16—H16C109.5
O13—C13—C12121.42 (14)H16B—C16—H16C109.5
C14—C13—C12119.23 (14)O13—C17—H17A109.5
O12—C12—C11123.83 (15)O13—C17—H17B109.5
O12—C12—C13115.82 (14)H17A—C17—H17B109.5
C11—C12—C13120.35 (15)O13—C17—H17C109.5
C15—C10—C11121.32 (15)H17A—C17—H17C109.5
C15—C10—N119.60 (14)H17B—C17—H17C109.5
C11—C10—N119.08 (15)O5—C19—H1A109.5
C7—C6—C5121.68 (17)O5—C19—H1B109.5
C7—C6—H3119.2H1A—C19—H1B109.5
C5—C6—H3119.2O5—C19—H1C109.5
C4—C5—O5125.46 (16)H1A—C19—H1C109.5
C4—C5—C6121.44 (16)H1B—C19—H1C109.5
O5—C5—C6113.10 (16)

Table 1 Arene C—H··· arene π interactions between screw-related molecules

Interaction between C4—H of one molecule and the centroid of the six membered (C4 through C9) aromatic ring of the screw-related molecule

H··· ring-centroid distanceAngle between the H···ring-centroid line and the aromatic ring normal
3.035 (1) Å5.6 (3) °

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FL2291).

References

  • Enraf–Nonius (1994). CAD-4 EXPRESS Enraf–Nonius, Delft, The Netherlands.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Fuwa, H. & Sasaki, M. (2009). J. Org. Chem.74, 212–221. [PubMed]
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • Li, L. & Martins, A. (2003). Tetrahedron Lett 44, 5987–5990.
  • Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst.39, 453–457.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Suthar, B., Fowler, A., Jones, D. S. & Ogle, C. A. (2005). Acta Cryst. E61, o607–o608.

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