(Z)-3-(1H-Indol-3-yl)-2-(3,4,5-tri­methoxy­phen­yl)acrylonitrile

Narsimha Reddy Penthala; Sean Parkin; Peter A Crooks

doi:10.1107/S1600536812005855

. 2012 Feb 17;68(Pt 3):o729. doi: 10.1107/S1600536812005855

(Z)-3-(1H-Indol-3-yl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile

Narsimha Reddy Penthala ^a, Sean Parkin ^b, Peter A Crooks ^a,^*

PMCID: PMC3295500 PMID: 22412611

Abstract

In the title compound, C₂₀H₁₈N₂O₃, the C=C bond of the acrylonitrile group that links the indole and the 3,4,5-trimethoxyphenyl rings has Z geometry, with dihedral angles between the plane of the acrylonitrile unit and the planes of the benzene and indole ring systems of 21.96 (5) and 38.94 (7)°, respectively. The acrylonitrile group is planar (r.m.s. deviation from planarity = 0.037 Å). Molecules are linked into head-to-tail chains that propagate along the b-axis direction by bifurcated N—H⋯O intermolecular hydrogen bonds, which form an R ₁ ²(5) motif between the indole NH group and the two methoxy O atoms furthest from the nitrile group.

Related literature

For biological activity of similar acrylonitriles, see: Naruto et al. (1983 ▶); Ohsumi et al. (1998 ▶); Saczewski et al. (2004 ▶). For the molecular structures of (E)-3-(benzo[b]thiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile and (Z)-3-(benzo[b]thiophen-2-yl)-2-(3,4-dimethoxyphenyl)acrylonitrile, see: Sonar et al. (2007 ▶). For the structure of (Z)-4-[3-(2,5-dioxoimidazolidin-4-ylidenemethyl)-1H-indol-1-ylmethyl]benzonitrile, see: Penthala et al. (2008 ▶).

Experimental

Crystal data

C₂₀H₁₈N₂O₃
M _r = 334.36
Monoclinic,
a = 11.3384 (4) Å
b = 21.1383 (8) Å
c = 6.9570 (3) Å
β = 93.610 (2)°
V = 1664.11 (11) Å³
Z = 4
Cu Kα radiation
μ = 0.74 mm⁻¹
T = 90 K
0.24 × 0.07 × 0.02 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.843, T _max = 0.929
20812 measured reflections
2979 independent reflections
2679 reflections with I > 2σ(I)
R _int = 0.053

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.097
S = 1.07
2979 reflections
233 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97 and local procedures.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812005855/nk2125sup1.cif

e-68-0o729-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812005855/nk2125Isup2.hkl

e-68-0o729-Isup2.hkl^{(146.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812005855/nk2125Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O2ⁱ	0.851 (18)	2.075 (18)	2.8635 (15)	153.8 (16)
N1—H1N⋯O3ⁱ	0.851 (18)	2.301 (17)	2.9476 (15)	133.0 (15)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This investigation was supported by NIH/National Cancer Institute grant RO1 CA140409.

supplementary crystallographic information

Comment

A number of 2,3-diarylacrylonitrile analogs have been found to possess interesting biological properties such as spasmolytic (Naruto et al., 1983), and cytotoxic activities (Ohsumi et al., 1998 and Saczewski et al., 2004). Previously, we have reported on the crystallographic data of benzothiophene acrylonitrile analogs (Sonar et al., 2007). In continuation of the synthesis of structurally related analogs and to compare the structure–activity relationships of different substituted acrylonitrile analogs, we have now prepared the title compound, (I), by the reaction of indole-3-carbaldehyde with (3,4,5-trimethoxyphenyl)acetonitrile in methanolic sodium methoxide at reflux temperature. Recrystallization from methanol afforded yellow needles of (I) that were suitable for X-ray analysis. The X-ray studies revealed that the title compound is the Z isomer. The olefinic bond linking the indole ring and the 3,4,5-trimethoxyphenyl units has a planar atomic arrangement. The r.m.s. deviation from the mean plane passing through atoms of C1–C2–C3–C8–N1 is 0.0133 Å. The acrylonitrile group is planar (r.m.s. deviation from planarity is 0.037 Å). In the trimethoxyphenyl group, one methyl is essentially in the plane of the benzene ring and the three O atoms [deviation = 0.0253 (18) Å]. The middle methyl has the largest [deviation = 1.0600 (17) Å], while the methyl that is on the same side as the nitrile group is in between [0.3788 (19)Å out of plane]. Significant deviations from the ideal bond-angle geometry around the Csp² atoms of the double bond are observed. The C1–C2–C3 and C1–C2–C9, C4–C3–C2 and C8–C3–C2 bond angles [105.88 (12)°, 127.93 (13)°, 134.18 (13)°, 106.90 (12)°, respectively] are distorted owing to steric hindrance around the double bond linking the two ring systems. Neither the indole ring nor the benzene ring of the 3,4,5-trimethoxyphenyl group is coplanar with the vinyl double bond, making dihedral angles of 38.94 (7)° and 21.96 (5)° respectively. Molecules are linked into head-to-tail chains that propagate along the b axis direction by bifurcated N—H···O intermolecular hydrogen bonds that form an R²₁(5) motif between the indole NH and the two methoxy O atoms furthest from the nitrile group, as shown in Figure 2.

Experimental

A mixture of indole-3-carbaldehyde (0.3 g, 2.06 mmol), and 2-(3,4,5-trimethoxyphenyl)acetonitrile (0.45 g, 2.17 mmol) were refluxed in methanolic 5% sodium methoxide solution for 5 hrs. The reaction mixture was cooled to room temperature and added to ice–cold water to afford a yellow crude solid, which was collected by filtration, washed with a 1:1 mixture of cold water and methanol, and suction–dried to afford the crude product. Crystallization during slow evaporation of methanol gave a yellow crystalline product of (Z)-3-(1H-indol-3-yl)-2- (3,4,5-trimethoxyphenyl)acrylonitrile that was suitable for X-ray crystallographic analysis. ¹H NMR (CDCl₃): δ 3.91 (s, 3H), 3.93 (s, 6H), 6.89 (s, 2H), 7.26–7.35 (m, 2H), 7.47–7.50 (d, 1H), 7.79 (s, 1H), 7.81 (s, 1H), 8.45–8.46 (d, 1H), 8.91 (bs, 1H, NH); ¹³C NMR (CDCl₃): δ 56.57, 61.28, 102.92, 105.11, 106.03, 111.83, 112.91, 121.19, 121.75, 125.77, 127.47, 129.27, 130.94, 132.38, 138.19, 153.76.