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

Monroe, T.B.; Rimland, C.; Moazami, Y.; Jones, D.S.; Ogle, C.A.

doi:10.1107/S1600536810018568

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 7| July 2010| Page o1678

doi:10.1107/S1600536810018568

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

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

^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 ). For pharmaceutical applications of indoles, see: Fuwa & Sasaki (2009 ); Li & Martins (2003 ).

Experimental

Crystal data

C₁₈H₁₉NO₄
M_r = 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)
R_int = 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
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 ).

Supporting information

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

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

checkCIF report

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)

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

	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

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

Crystal data top

C₁₈H₁₉NO₄	F(000) = 1328
M_r = 313.34	D_x = 1.273 Mg m⁻³
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: -C 2yc	Cell parameters from 24 reflections
a = 19.0036 (16) Å	θ = 6.4–20.8°
b = 7.3179 (14) Å	µ = 0.74 mm⁻¹
c = 23.672 (4) Å	T = 295 K
β = 96.802 (10)°	Prism, colorless
V = 3268.8 (9) Å³	0.32 × 0.27 × 0.26 mm
Z = 8

Data collection top

Enraf–Nonius CAD-4 diffractometer	θ_max = 67.4°, θ_min = 3.8°
non–profiled ω/2θ scans	h = −22→22
6084 measured reflections	k = −8→0
2951 independent reflections	l = −28→28
2074 reflections with I > 2σ(I)	3 standard reflections every 190 reflections
R_int = 0.026	intensity decay: 4%

Refinement top

Refinement on F²	H-atom parameters constrained
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0613P)² + 0.605P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.037	(Δ/σ)_max < 0.001
wR(F²) = 0.110	Δρ_max = 0.16 e Å⁻³
S = 1.00	Δρ_min = −0.16 e Å⁻³
2951 reflections	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
209 parameters	Extinction coefficient: 0.00188 (13)
0 restraints

Crystal data top

C₁₈H₁₉NO₄	V = 3268.8 (9) Å³
M_r = 313.34	Z = 8
Monoclinic, C2/c	Cu Kα radiation
a = 19.0036 (16) Å	µ = 0.74 mm⁻¹
b = 7.3179 (14) Å	T = 295 K
c = 23.672 (4) Å	0.32 × 0.27 × 0.26 mm
β = 96.802 (10)°

Data collection top

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

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.110	H-atom parameters constrained
S = 1.00	Δρ_max = 0.16 e Å⁻³
2951 reflections	Δρ_min = −0.16 e Å⁻³
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

	x	y	z	U_iso*/U_eq
O14	0.15356 (6)	0.12928 (15)	0.49143 (5)	0.0511 (3)
O13	0.07247 (7)	0.29172 (17)	0.40657 (5)	0.0575 (3)
O5	0.40130 (7)	0.77324 (19)	0.74372 (5)	0.0647 (4)
N	0.14855 (7)	0.67340 (19)	0.60827 (5)	0.0451 (3)
O12	0.02905 (7)	0.64188 (17)	0.41594 (5)	0.0562 (4)
C11	0.08846 (8)	0.6630 (2)	0.51210 (7)	0.0459 (4)
H15	0.0741	0.7834	0.5159	0.055*
C15	0.15105 (8)	0.3970 (2)	0.55189 (6)	0.0429 (4)
H11	0.1773	0.3391	0.5824	0.051*
C14	0.13334 (8)	0.3050 (2)	0.50087 (7)	0.0414 (4)
C8	0.21611 (9)	0.6831 (2)	0.63793 (6)	0.0428 (4)
C7	0.27934 (9)	0.6005 (2)	0.62755 (7)	0.0488 (4)
H4	0.2813	0.5235	0.5965	0.059*
C13	0.09214 (8)	0.3894 (2)	0.45562 (6)	0.0430 (4)
C12	0.06941 (8)	0.5691 (2)	0.46185 (7)	0.0435 (4)
C10	0.12910 (8)	0.5758 (2)	0.55666 (6)	0.0427 (4)
C6	0.33859 (10)	0.6368 (3)	0.66472 (7)	0.0519 (4)
H3	0.3813	0.5823	0.6589	0.062*
C5	0.33640 (10)	0.7540 (2)	0.71127 (7)	0.0496 (4)
C3	0.14176 (10)	0.8679 (2)	0.68041 (7)	0.0539 (5)
H9	0.124	0.95	0.7052	0.065*
C18	0.20053 (9)	0.0443 (2)	0.53514 (7)	0.0532 (4)
H18A	0.2109	−0.0777	0.5237	0.08*
H18B	0.1786	0.04	0.5696	0.08*
H18C	0.2437	0.1134	0.5415	0.08*
C4	0.27495 (10)	0.8393 (2)	0.72137 (7)	0.0520 (4)
H7	0.274	0.9179	0.7521	0.062*
C2	0.10450 (10)	0.7872 (2)	0.63464 (7)	0.0512 (4)
H8	0.0566	0.8057	0.6228	0.061*
C9	0.21305 (9)	0.8044 (2)	0.68373 (7)	0.0466 (4)
C16	0.00926 (10)	0.8294 (3)	0.41920 (8)	0.0597 (5)
H16A	−0.0187	0.8644	0.3844	0.09*
H16B	0.0511	0.9038	0.4248	0.09*
H16C	−0.0179	0.8461	0.4505	0.09*
C17	0.10615 (13)	0.3480 (3)	0.35877 (8)	0.0751 (6)
H17A	0.0895	0.2739	0.3265	0.113*
H17B	0.1565	0.3342	0.3673	0.113*
H17C	0.0951	0.4738	0.3504	0.113*
C19	0.40555 (13)	0.8959 (3)	0.78968 (9)	0.0857 (7)
H1A	0.4531	0.8973	0.8086	0.129*
H1B	0.3736	0.858	0.8159	0.129*
H1C	0.3929	1.0162	0.7759	0.129*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O14	0.0641 (7)	0.0342 (6)	0.0528 (7)	0.0029 (5)	−0.0026 (6)	−0.0024 (5)
O13	0.0760 (8)	0.0458 (7)	0.0466 (6)	−0.0098 (6)	−0.0091 (6)	−0.0038 (5)
O5	0.0659 (8)	0.0628 (9)	0.0605 (8)	−0.0043 (7)	−0.0125 (6)	−0.0102 (7)
N	0.0516 (8)	0.0402 (8)	0.0423 (7)	0.0020 (6)	0.0006 (6)	−0.0044 (6)
O12	0.0620 (8)	0.0452 (7)	0.0560 (7)	0.0041 (6)	−0.0155 (6)	0.0022 (6)
C11	0.0497 (9)	0.0362 (9)	0.0503 (9)	0.0013 (7)	0.0003 (7)	−0.0013 (7)
C15	0.0465 (9)	0.0387 (9)	0.0420 (8)	−0.0023 (7)	−0.0006 (7)	0.0026 (7)
C14	0.0443 (8)	0.0322 (8)	0.0475 (8)	−0.0049 (7)	0.0050 (7)	0.0006 (7)
C8	0.0522 (9)	0.0359 (9)	0.0394 (8)	−0.0001 (7)	0.0009 (7)	−0.0006 (7)
C7	0.0568 (10)	0.0445 (10)	0.0446 (8)	0.0004 (8)	0.0043 (7)	−0.0065 (7)
C13	0.0468 (9)	0.0386 (9)	0.0421 (8)	−0.0093 (7)	−0.0016 (7)	−0.0018 (7)
C12	0.0409 (8)	0.0398 (9)	0.0480 (9)	−0.0034 (7)	−0.0027 (7)	0.0044 (7)
C10	0.0458 (8)	0.0383 (9)	0.0431 (8)	−0.0040 (7)	0.0021 (7)	−0.0025 (7)
C6	0.0531 (10)	0.0494 (10)	0.0528 (10)	0.0010 (8)	0.0044 (8)	−0.0033 (8)
C5	0.0589 (10)	0.0424 (10)	0.0452 (9)	−0.0040 (8)	−0.0040 (8)	0.0020 (7)
C3	0.0648 (11)	0.0459 (10)	0.0505 (9)	0.0095 (8)	0.0050 (8)	−0.0088 (8)
C18	0.0551 (10)	0.0418 (10)	0.0619 (10)	0.0023 (8)	0.0034 (8)	0.0063 (8)
C4	0.0704 (12)	0.0417 (10)	0.0423 (8)	−0.0013 (9)	−0.0001 (8)	−0.0072 (7)
C2	0.0560 (10)	0.0448 (9)	0.0523 (9)	0.0092 (8)	0.0044 (8)	−0.0017 (8)
C9	0.0608 (10)	0.0371 (9)	0.0409 (8)	0.0014 (8)	0.0022 (7)	−0.0016 (7)
C16	0.0653 (12)	0.0456 (11)	0.0654 (12)	0.0073 (9)	−0.0046 (9)	0.0097 (9)
C17	0.1107 (18)	0.0663 (14)	0.0487 (10)	0.0058 (13)	0.0109 (11)	−0.0032 (10)
C19	0.0995 (17)	0.0828 (17)	0.0663 (13)	0.0018 (14)	−0.0254 (12)	−0.0217 (12)

Geometric parameters (Å, º) top

O14—C14	1.368 (2)	C13—C12	1.397 (2)
O14—C18	1.427 (2)	C6—C5	1.401 (2)
O13—C13	1.3769 (18)	C6—H3	0.93
O13—C17	1.425 (2)	C5—C4	1.370 (2)
O5—C5	1.381 (2)	C3—C2	1.357 (2)
O5—C19	1.405 (2)	C3—C9	1.426 (2)
N—C2	1.381 (2)	C3—H9	0.93
N—C8	1.390 (2)	C18—H18A	0.96
N—C10	1.4255 (19)	C18—H18B	0.96
O12—C12	1.3622 (18)	C18—H18C	0.96
O12—C16	1.427 (2)	C4—C9	1.412 (2)
C11—C12	1.384 (2)	C4—H7	0.93
C11—C10	1.387 (2)	C2—H8	0.93
C11—H15	0.93	C16—H16A	0.96
C15—C10	1.382 (2)	C16—H16B	0.96
C15—C14	1.389 (2)	C16—H16C	0.96
C15—H11	0.93	C17—H17A	0.96
C14—C13	1.394 (2)	C17—H17B	0.96
C8—C7	1.393 (2)	C17—H17C	0.96
C8—C9	1.408 (2)	C19—H1A	0.96
C7—C6	1.371 (2)	C19—H1B	0.96
C7—H4	0.93	C19—H1C	0.96

C14—O14—C18	117.06 (12)	C2—C3—C9	107.72 (15)
C13—O13—C17	114.63 (14)	C2—C3—H9	126.1
C5—O5—C19	117.49 (16)	C9—C3—H9	126.1
C2—N—C8	108.29 (13)	O14—C18—H18A	109.5
C2—N—C10	125.44 (14)	O14—C18—H18B	109.5
C8—N—C10	126.06 (14)	H18A—C18—H18B	109.5
C12—O12—C16	117.38 (13)	O14—C18—H18C	109.5
C12—C11—C10	119.38 (15)	H18A—C18—H18C	109.5
C12—C11—H15	120.3	H18B—C18—H18C	109.5
C10—C11—H15	120.3	C5—C4—C9	118.11 (15)
C10—C15—C14	119.05 (15)	C5—C4—H7	120.9
C10—C15—H11	120.5	C9—C4—H7	120.9
C14—C15—H11	120.5	C3—C2—N	109.65 (16)
O14—C14—C15	123.64 (14)	C3—C2—H8	125.2
O14—C14—C13	115.72 (14)	N—C2—H8	125.2
C15—C14—C13	120.63 (15)	C8—C9—C4	119.51 (16)
N—C8—C7	130.78 (15)	C8—C9—C3	106.80 (15)
N—C8—C9	107.54 (14)	C4—C9—C3	133.69 (16)
C7—C8—C9	121.66 (15)	O12—C16—H16A	109.5
C6—C7—C8	117.58 (16)	O12—C16—H16B	109.5
C6—C7—H4	121.2	H16A—C16—H16B	109.5
C8—C7—H4	121.2	O12—C16—H16C	109.5
O13—C13—C14	119.30 (15)	H16A—C16—H16C	109.5
O13—C13—C12	121.42 (14)	H16B—C16—H16C	109.5
C14—C13—C12	119.23 (14)	O13—C17—H17A	109.5
O12—C12—C11	123.83 (15)	O13—C17—H17B	109.5
O12—C12—C13	115.82 (14)	H17A—C17—H17B	109.5
C11—C12—C13	120.35 (15)	O13—C17—H17C	109.5
C15—C10—C11	121.32 (15)	H17A—C17—H17C	109.5
C15—C10—N	119.60 (14)	H17B—C17—H17C	109.5
C11—C10—N	119.08 (15)	O5—C19—H1A	109.5
C7—C6—C5	121.68 (17)	O5—C19—H1B	109.5
C7—C6—H3	119.2	H1A—C19—H1B	109.5
C5—C6—H3	119.2	O5—C19—H1C	109.5
C4—C5—O5	125.46 (16)	H1A—C19—H1C	109.5
C4—C5—C6	121.44 (16)	H1B—C19—H1C	109.5
O5—C5—C6	113.10 (16)

Experimental details

Crystal data
Chemical formula	C₁₈H₁₉NO₄
M_r	313.34
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	295
a, b, c (Å)	19.0036 (16), 7.3179 (14), 23.672 (4)
β (°)	96.802 (10)
V (Å³)	3268.8 (9)
Z	8
Radiation type	Cu Kα
µ (mm⁻¹)	0.74
Crystal size (mm)	0.32 × 0.27 × 0.26

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6084, 2951, 2074
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.599

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.110, 1.00
No. of reflections	2951
No. of parameters	209
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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 distance	Angle between the H···ring-centroid line and the aromatic ring normal
3.035 (1) Å	5.6 (3) °

Acknowledgements

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

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