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

Thomas Blake Monroe; Casey Rimland; Yasamin Moazami; Daniel S Jones; Craig A Ogle

doi:10.1107/S1600536810018568

. 2010 Jun 16;66(Pt 7):o1678. doi: 10.1107/S1600536810018568

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

Thomas Blake Monroe ^a, Casey Rimland ^a, Yasamin Moazami ^a, Daniel S Jones ^a,^*, Craig A Ogle ^a,^*

PMCID: PMC3007039 PMID: 21587903

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 ▶). For pharmaceutical applications of indoles, see: Fuwa & Sasaki (2009 ▶); Li & Martins (2003 ▶). graphic file with name e-66-o1678-scheme1.jpg

Experimental

Crystal data

C₁₈H₁₉NO₄
M _r = 313.34
Monoclinic,
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
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; 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 ▶).

Supplementary Material

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

e-66-o1678-sup1.cif^{(16.8KB, cif)}

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

e-66-o1678-Isup2.hkl^{(142KB, 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)