organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

aDepartment of Chemistry, The University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA
*Correspondence e-mail: djones@uncc.edu, cogle@uncc.edu

(Received 22 January 2010; accepted 18 May 2010; online 16 June 2010)

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[Suthar, B., Fowler, A., Jones, D. S. & Ogle, C. A. (2005). Acta Cryst. E61, o607-o608.]). For pharmaceutical applications of indoles, see: Fuwa & Sasaki (2009[Fuwa, H. & Sasaki, M. (2009). J. Org. Chem. 74, 212-221.]); Li & Martins (2003[Li, L. & Martins, A. (2003). Tetrahedron Lett. 44, 5987-5990.]).

[Scheme 1]

Experimental

Crystal data
  • C18H19NO4

  • Mr = 313.34

  • Monoclinic, C 2/c

  • 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)

  • Rint = 0.026

  • 3 standard reflections every 190 reflections intensity decay: 4%

Refinement
  • R[F2 > 2σ(F2)] = 0.037

  • wR(F2) = 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[Enraf-Nonius (1994). CAD-4 EXPRESS. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]), Mercury (Macrae et al., 2006[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.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).

Supporting information


Comment top

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)°.

Related literature top

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

Experimental top

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 top

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.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997), Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. View of the title compound (50% probability displacement ellipsoids)
[Figure 2] Fig. 2. Packing diagram showing the arene C—H···π interactions between molecules related by a two-fold screw axis
[Figure 3] Fig. 3. Synthesis scheme
5-Methoxy-1-(3,4,5-trimethoxyphenyl)-1H-indole top
Crystal data top
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 top
Enraf–Nonius CAD-4
diffractometer
θmax = 67.4°, θmin = 3.8°
non–profiled ω/2θ scansh = 2222
6084 measured reflectionsk = 80
2951 independent reflectionsl = 2828
2074 reflections with I > 2σ(I)3 standard reflections every 190 reflections
Rint = 0.026 intensity decay: 4%
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full w = 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
Crystal data top
C18H19NO4V = 3268.8 (9) Å3
Mr = 313.34Z = 8
Monoclinic, C2/cCu Kα radiation
a = 19.0036 (16) ŵ = 0.74 mm1
b = 7.3179 (14) ÅT = 295 K
c = 23.672 (4) Å0.32 × 0.27 × 0.26 mm
β = 96.802 (10)°
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.026
6084 measured reflections3 standard reflections every 190 reflections
2951 independent reflections intensity decay: 4%
2074 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0370 restraints
wR(F2) = 0.110H-atom parameters constrained
S = 1.00Δρmax = 0.16 e Å3
2951 reflectionsΔρmin = 0.16 e Å3
209 parameters
Special details top

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) top
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)
H18A0.21090.07770.52370.08*
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)
H16A0.01870.86440.38440.09*
H16B0.05110.90380.42480.09*
H16C0.01790.84610.45050.09*
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) top
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, º) top
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)

Experimental details

Crystal data
Chemical formulaC18H19NO4
Mr313.34
Crystal system, space groupMonoclinic, C2/c
Temperature (K)295
a, b, c (Å)19.0036 (16), 7.3179 (14), 23.672 (4)
β (°) 96.802 (10)
V3)3268.8 (9)
Z8
Radiation typeCu Kα
µ (mm1)0.74
Crystal size (mm)0.32 × 0.27 × 0.26
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
6084, 2951, 2074
Rint0.026
(sin θ/λ)max1)0.599
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.110, 1.00
No. of reflections2951
No. of parameters209
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.16, 0.16

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), Mercury (Macrae et al., 2006), WinGX (Farrugia, 1999).

Arene C—H··· arene π interactions between screw-related molecules top
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) °
 

Acknowledgements

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

References

First citationEnraf–Nonius (1994). CAD-4 EXPRESS. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
First citationFarrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.  CrossRef CAS IUCr Journals Google Scholar
First citationFuwa, H. & Sasaki, M. (2009). J. Org. Chem. 74, 212–221.  Web of Science CrossRef PubMed CAS Google Scholar
First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
First citationLi, L. & Martins, A. (2003). Tetrahedron Lett. 44, 5987–5990.  Web of Science CrossRef CAS Google Scholar
First citationMacrae, 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.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSuthar, B., Fowler, A., Jones, D. S. & Ogle, C. A. (2005). Acta Cryst. E61, o607–o608.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar

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