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Acta Cryst. (2008). E64, o2122    [ doi:10.1107/S1600536808032601 ]

(Z)-4-[3-(2,5-Dioxoimidazolidin-4-ylidenemethyl)-1H-indol-1-ylmethyl]benzonitrile

N. R. Penthala, T. R. Y. Reddy, S. Parkin and P. A. Crooks

Abstract top

In the title compound, C20H14N4O2, molecules are linked into chains by N-H...O hydrogen bonds, but the cyano group does not participate in the supramolecular aggregation. The crystal structure of the compound indicates the presence of a double bond with Z geometry, connecting the imidazolidine and indole units. The dihedral angle between the imidazole and benzene ring planes is 62.45 (4)°.

Comment top

As part of a continuing search for biologically active molecules containing indole ring systems (Sonar et al., 2007), we have now prepared the title compound by the reaction of 4-(3-formyl-1H-indol-1-ylmethyl)benzonitrile with imidazolidine-2,4-dione in the presence of ammonium acetate in acetic acid at 393 K. The compound was crystallized from a mixture of methanol and ethylacetate. The molecular structure and the atom-numbering scheme are shown in Fig.1. The indole ring is planar with bond distances and angles comparable with those previously reported for other indole derivatives (Mason et al., 2003; Zarza, et al., 1988). The X-ray studies revealed that the obtained compound is the Z isomer. The C18—C19 bond is in a trans position with respect to the C2—C17 bond. The olefinic bond (C17=C18) has a planar atomic arrangement, since the r.m.s. deviation from the mean plane passing through atoms C2, C17, C18, N4 is 0.0009 (5) Å. The maximum deviation from plane for imidazoline ring is 0.0087 Å. Deviations from ideal geometry are observed in the bond angles around atoms C2, C17 and C18. The C17=C18—C19 bond angle is close to the standard planar triangular value of 120°, whereas the C1=C2—C17, C18—C17=C2 and C17=C18—N4 bond angles are more distorted due to the strain induced by the C17=C18—C1=O1 conjugated double bond linkage. These bond angle deformations, which require little energy, are needed to release the intramolecular interactions between non-bonded atoms. The imidazolidine ring, which makes a dihedral angle of 2.48 (5)° with the adjacent aromatic ring presents very small distortions around atoms N4, C20, N3 and C19.

Significant intermolecular hydrogen-bonding interactions are found between N(3)—H(3)···O(1) and N(4)—H(4)···O(2). Molecules are linked into chains by a series of N—H···O hydrogen bonds.

Related literature top

For 2-indol-3-yl-methylenequinuclidin-3-ols NADPH oxidase activity, see: Sekhar et al. (2003). For novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007). For the molecular structures of di- and triindolylmethanes, see: Mason et al. (2003). For the structures of 1H-indole-3-ethylene-3'-methoxysalicylaldimine and 3-[3'-azapentyl-3'-en-4'-(2''-hydroxyphenyl)]indole, see: Zarza et al. (1988).

Experimental top

A mixture of 4-(3-formyl-indol-1-ylmethyl)benzonitrile (0.5 g, 1.92 mmol), imidazolidine-2,4-dione (0.23 g, 2.30 mmol) and ammonium acetate (0.15 g, 1.94 mmol) was stirred in acetic acid (5 ml) at 393 K for 10 hrs. The reaction mixture was cooled to room temperature and the yellow solid that separated was collected by filtration, washed with cold water and dried to afford the the crude product. Crystallization from methanol and ethyl acetate (1:1) gave a yellow crystalline product of (Z)-4-((3-((2,5- dioxoimidazolidin-4-ylidene)methyl)-1H-indol-1-yl)methyl) benzonitrile that was suitable for X-ray analysis. 1H NMR (DMSO d6): δ 5.56 (s, 2H), 6.7 (s, 1H), 7.13–7.23 (m, 2H), 7.44–7.53 (m, 3H), 7.79–7.83 (m, 3H), 8.30 (s, 1H), 10.15 (bs, 1H), 11.07 (bs, 1H); 13C NMR (DMSO d6): δ 101.46, 109.25, 111.06, 111.22, 119.21, 119.29, 121.34, 123.42, 124.95, 128.10, 128.70, 130.63, 133.26, 136.25, 143.71, 155.94, 165.87.

Refinement top

H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained distances of 0.99 Å (R2CH2), 0.95 Å (R2CH) and 0.88 Å (NH) with Uiso(H) values set to 1.2Ueq of the attached atom.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006); data reduction: APEX2 (Bruker, 2006); 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: SHELX97 (Sheldrick, 2008) and local procedures.

Figures top
[Figure 1] Fig. 1. A view of the molecule with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
(Z)-4-[3-(2,5-Dioxoimidazolidin-4-ylidenemethyl)-1H-indol- 1-ylmethyl]benzonitrile top
Crystal data top
C20H14N4O2F(000) = 1424
Mr = 342.35Dx = 1.383 Mg m−3
Monoclinic, C2/cCu Kα radiation, λ = 1.54178 Å
Hall symbol: -C 2ycCell parameters from 9981 reflections
a = 18.8495 (16) Åθ = 3.9–68.8°
b = 7.6812 (7) ŵ = 0.76 mm−1
c = 24.322 (2) ÅT = 90 K
β = 110.939 (3)°Block, yellow
V = 3289.0 (5) Å30.15 × 0.08 × 0.06 mm
Z = 8
Data collection top
Bruker X8 Proteum
diffractometer		3025 independent reflections
Radiation source: fine-focus rotating anode2849 reflections with I > 2σ(I)
graded multilayer opticsRint = 0.039
Detector resolution: 18 pixels mm-1θmax = 68.8°, θmin = 3.9°
φ and ω scansh = −22→22
Absorption correction: multi-scan
(SADABS in APEX2; Bruker, 2006)		k = −9→9
Tmin = 0.806, Tmax = 0.957l = −28→29
23493 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.034H-atom parameters constrained
wR(F2) = 0.088 w = 1/[σ2(Fo2) + (0.043P)2 + 2.7005P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
3025 reflectionsΔρmax = 0.24 e Å−3
236 parametersΔρmin = −0.30 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.00030 (6)
Crystal data top
C20H14N4O2V = 3289.0 (5) Å3
Mr = 342.35Z = 8
Monoclinic, C2/cCu Kα radiation
a = 18.8495 (16) ŵ = 0.76 mm−1
b = 7.6812 (7) ÅT = 90 K
c = 24.322 (2) Å0.15 × 0.08 × 0.06 mm
β = 110.939 (3)°
Data collection top
Bruker X8 Proteum
diffractometer		3025 independent reflections
Absorption correction: multi-scan
(SADABS in APEX2; Bruker, 2006)		2849 reflections with I > 2σ(I)
Tmin = 0.806, Tmax = 0.957Rint = 0.039
23493 measured reflectionsθmax = 68.8°
Refinement top
R[F2 > 2σ(F2)] = 0.034H-atom parameters constrained
wR(F2) = 0.088Δρmax = 0.24 e Å−3
S = 1.04Δρmin = −0.30 e Å−3
3025 reflectionsAbsolute structure: ?
236 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.41106 (5)0.49108 (13)0.60476 (4)0.0204 (2)
N20.28685 (7)0.12998 (16)0.84996 (5)0.0344 (3)
N30.66684 (5)0.16845 (13)0.50768 (4)0.0204 (2)
H30.70100.12480.49460.024*
N40.56545 (5)0.18829 (13)0.53212 (4)0.0213 (2)
H40.52320.16120.53770.026*
O10.71827 (4)0.44259 (11)0.53352 (4)0.0233 (2)
O20.58759 (5)−0.07063 (12)0.49259 (4)0.0300 (2)
C10.46081 (6)0.41065 (15)0.58406 (5)0.0196 (2)
H10.45490.29600.56840.024*
C20.52091 (6)0.51930 (15)0.58903 (5)0.0185 (2)
C30.50688 (6)0.67773 (15)0.61526 (5)0.0201 (2)
C40.54595 (7)0.83512 (16)0.63133 (6)0.0269 (3)
H4A0.59280.85350.62570.032*
C50.51500 (8)0.96293 (17)0.65546 (7)0.0343 (3)
H50.54121.07030.66680.041*
C60.44596 (8)0.93872 (17)0.66367 (6)0.0337 (3)
H60.42631.02980.68050.040*
C70.40588 (7)0.78571 (17)0.64794 (6)0.0271 (3)
H70.35870.76930.65310.033*
C80.43762 (6)0.65602 (15)0.62406 (5)0.0210 (3)
C90.33815 (6)0.41858 (17)0.60065 (5)0.0235 (3)
H9A0.32450.32590.57040.028*
H9B0.29930.51120.58690.028*
C100.33468 (6)0.34369 (15)0.65670 (5)0.0199 (3)
C110.27885 (7)0.22088 (16)0.65210 (5)0.0245 (3)
H110.24870.17710.61450.029*
C120.26669 (7)0.16176 (16)0.70142 (6)0.0264 (3)
H120.22800.07860.69790.032*
C130.31168 (7)0.22512 (15)0.75657 (5)0.0225 (3)
C140.36964 (7)0.34280 (15)0.76188 (5)0.0222 (3)
H140.40130.38300.79960.027*
C150.38107 (6)0.40105 (15)0.71200 (5)0.0216 (3)
H150.42090.48090.71550.026*
C160.29783 (7)0.17006 (16)0.80831 (5)0.0266 (3)
C170.58384 (6)0.49104 (15)0.57005 (5)0.0194 (2)
H170.61770.58660.57550.023*
C180.60159 (6)0.34914 (15)0.54582 (5)0.0186 (2)
C190.66927 (6)0.33333 (15)0.52922 (5)0.0190 (2)
C200.60397 (6)0.07873 (16)0.50901 (5)0.0220 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0187 (5)0.0246 (5)0.0217 (5)−0.0014 (4)0.0117 (4)−0.0015 (4)
N20.0372 (6)0.0407 (7)0.0285 (6)−0.0136 (5)0.0156 (5)−0.0019 (5)
N30.0167 (5)0.0266 (5)0.0216 (5)−0.0027 (4)0.0116 (4)−0.0056 (4)
N40.0171 (5)0.0257 (5)0.0260 (5)−0.0045 (4)0.0137 (4)−0.0056 (4)
O10.0205 (4)0.0268 (4)0.0277 (4)−0.0048 (3)0.0148 (3)−0.0036 (3)
O20.0242 (4)0.0301 (5)0.0419 (5)−0.0081 (4)0.0195 (4)−0.0151 (4)
C10.0207 (5)0.0222 (6)0.0190 (5)0.0000 (4)0.0109 (4)−0.0021 (4)
C20.0182 (5)0.0215 (6)0.0168 (5)0.0010 (4)0.0076 (4)0.0007 (4)
C30.0206 (6)0.0215 (6)0.0198 (5)0.0015 (4)0.0091 (4)0.0025 (4)
C40.0268 (6)0.0223 (6)0.0354 (7)−0.0011 (5)0.0156 (5)0.0008 (5)
C50.0384 (7)0.0207 (6)0.0477 (8)−0.0023 (5)0.0201 (6)−0.0046 (6)
C60.0387 (8)0.0240 (7)0.0440 (8)0.0065 (5)0.0215 (6)−0.0037 (6)
C70.0270 (6)0.0275 (6)0.0318 (7)0.0052 (5)0.0166 (5)0.0017 (5)
C80.0217 (6)0.0218 (6)0.0213 (6)0.0019 (4)0.0100 (5)0.0022 (4)
C90.0181 (5)0.0327 (7)0.0223 (6)−0.0031 (5)0.0104 (5)−0.0015 (5)
C100.0180 (5)0.0214 (6)0.0237 (6)0.0021 (4)0.0115 (5)−0.0017 (4)
C110.0230 (6)0.0280 (6)0.0239 (6)−0.0048 (5)0.0102 (5)−0.0050 (5)
C120.0255 (6)0.0272 (6)0.0296 (6)−0.0080 (5)0.0137 (5)−0.0026 (5)
C130.0242 (6)0.0225 (6)0.0242 (6)0.0004 (5)0.0128 (5)0.0012 (5)
C140.0228 (6)0.0219 (6)0.0222 (6)−0.0005 (4)0.0083 (5)−0.0016 (4)
C150.0192 (5)0.0216 (6)0.0255 (6)−0.0021 (4)0.0100 (5)−0.0005 (5)
C160.0270 (6)0.0277 (6)0.0267 (6)−0.0060 (5)0.0118 (5)−0.0018 (5)
C170.0174 (5)0.0234 (6)0.0190 (5)−0.0025 (4)0.0083 (4)0.0006 (4)
C180.0163 (5)0.0238 (6)0.0171 (5)−0.0012 (4)0.0078 (4)0.0002 (4)
C190.0180 (5)0.0252 (6)0.0156 (5)−0.0013 (4)0.0081 (4)−0.0006 (4)
C200.0186 (5)0.0275 (6)0.0225 (6)−0.0038 (5)0.0105 (4)−0.0061 (5)
Geometric parameters (Å, °) top
N1—C11.3608 (15)C6—C71.3754 (19)
N1—C81.3815 (15)C6—H60.9500
N1—C91.4527 (14)C7—C81.3913 (17)
N2—C161.1459 (17)C7—H70.9500
N3—C191.3650 (15)C9—C101.5025 (16)
N3—C201.3812 (15)C9—H9A0.9900
N3—H30.8800C9—H9B0.9900
N4—C201.3576 (15)C10—C111.3877 (17)
N4—C181.3926 (15)C10—C151.3883 (16)
N4—H40.8800C11—C121.3761 (17)
O1—C191.2246 (14)C11—H110.9500
O2—C201.2178 (15)C12—C131.3938 (17)
C1—C21.3772 (16)C12—H120.9500
C1—H10.9500C13—C141.3879 (17)
C2—C171.4348 (16)C13—C161.4372 (17)
C2—C31.4416 (16)C14—C151.3805 (17)
C3—C41.3967 (17)C14—H140.9500
C3—C81.4064 (16)C15—H150.9500
C4—C51.3759 (19)C17—C181.3372 (17)
C4—H4A0.9500C17—H170.9500
C5—C61.398 (2)C18—C191.4742 (15)
C5—H50.9500
C1—N1—C8109.16 (9)C10—C9—H9A108.4
C1—N1—C9124.09 (10)N1—C9—H9B108.4
C8—N1—C9126.44 (10)C10—C9—H9B108.4
C19—N3—C20111.43 (9)H9A—C9—H9B107.5
C19—N3—H3124.3C11—C10—C15119.39 (11)
C20—N3—H3124.3C11—C10—C9117.71 (10)
C20—N4—C18111.14 (9)C15—C10—C9122.75 (10)
C20—N4—H4124.4C12—C11—C10120.79 (11)
C18—N4—H4124.4C12—C11—H11119.6
N1—C1—C2110.27 (10)C10—C11—H11119.6
N1—C1—H1124.9C11—C12—C13119.35 (11)
C2—C1—H1124.9C11—C12—H12120.3
C1—C2—C17128.96 (11)C13—C12—H12120.3
C1—C2—C3105.97 (10)C14—C13—C12120.33 (11)
C17—C2—C3125.00 (10)C14—C13—C16119.57 (11)
C4—C3—C8119.03 (11)C12—C13—C16120.10 (11)
C4—C3—C2133.85 (11)C15—C14—C13119.62 (11)
C8—C3—C2107.12 (10)C15—C14—H14120.2
C5—C4—C3118.39 (12)C13—C14—H14120.2
C5—C4—H4A120.8C14—C15—C10120.43 (11)
C3—C4—H4A120.8C14—C15—H15119.8
C4—C5—C6121.63 (13)C10—C15—H15119.8
C4—C5—H5119.2N2—C16—C13178.46 (14)
C6—C5—H5119.2C18—C17—C2129.12 (11)
C7—C6—C5121.37 (12)C18—C17—H17115.4
C7—C6—H6119.3C2—C17—H17115.4
C5—C6—H6119.3C17—C18—N4130.58 (10)
C6—C7—C8116.92 (11)C17—C18—C19124.41 (10)
C6—C7—H7121.5N4—C18—C19104.99 (9)
C8—C7—H7121.5O1—C19—N3126.12 (10)
N1—C8—C7129.86 (11)O1—C19—C18128.34 (10)
N1—C8—C3107.48 (10)N3—C19—C18105.54 (9)
C7—C8—C3122.66 (11)O2—C20—N4127.55 (11)
N1—C9—C10115.55 (9)O2—C20—N3125.55 (11)
N1—C9—H9A108.4N4—C20—N3106.90 (10)
C8—N1—C1—C2−0.07 (13)C15—C10—C11—C123.09 (18)
C9—N1—C1—C2173.86 (10)C9—C10—C11—C12−172.46 (11)
N1—C1—C2—C17−176.56 (11)C10—C11—C12—C13−0.67 (19)
N1—C1—C2—C30.49 (13)C11—C12—C13—C14−1.89 (19)
C1—C2—C3—C4−179.90 (13)C11—C12—C13—C16177.54 (11)
C17—C2—C3—C4−2.7 (2)C12—C13—C14—C151.98 (18)
C1—C2—C3—C8−0.72 (12)C16—C13—C14—C15−177.45 (11)
C17—C2—C3—C8176.48 (10)C13—C14—C15—C100.48 (17)
C8—C3—C4—C50.24 (18)C11—C10—C15—C14−2.99 (17)
C2—C3—C4—C5179.34 (12)C9—C10—C15—C14172.32 (11)
C3—C4—C5—C6−0.4 (2)C1—C2—C17—C18−4.0 (2)
C4—C5—C6—C70.0 (2)C3—C2—C17—C18179.49 (11)
C5—C6—C7—C80.6 (2)C2—C17—C18—N4−0.3 (2)
C1—N1—C8—C7179.20 (12)C2—C17—C18—C19−178.46 (11)
C9—N1—C8—C75.45 (19)C20—N4—C18—C17−178.60 (12)
C1—N1—C8—C3−0.40 (12)C20—N4—C18—C19−0.22 (12)
C9—N1—C8—C3−174.15 (10)C20—N3—C19—O1179.92 (11)
C6—C7—C8—N1179.66 (12)C20—N3—C19—C180.11 (12)
C6—C7—C8—C3−0.79 (18)C17—C18—C19—O1−1.22 (19)
C4—C3—C8—N1−179.99 (10)N4—C18—C19—O1−179.74 (11)
C2—C3—C8—N10.69 (12)C17—C18—C19—N3178.58 (10)
C4—C3—C8—C70.38 (17)N4—C18—C19—N30.06 (11)
C2—C3—C8—C7−178.95 (11)C18—N4—C20—O2179.95 (12)
C1—N1—C9—C10103.89 (13)C18—N4—C20—N30.28 (13)
C8—N1—C9—C10−83.24 (14)C19—N3—C20—O2−179.91 (11)
N1—C9—C10—C11−157.33 (11)C19—N3—C20—N4−0.24 (13)
N1—C9—C10—C1527.28 (16)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H3···O1i0.881.952.8237 (12)173
N4—H4···O2ii0.882.072.8740 (13)151
Symmetry codes: (i) −x+3/2, −y+1/2, −z+1; (ii) −x+1, −y, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H3···O1i0.881.952.8237 (12)173
N4—H4···O2ii0.882.072.8740 (13)151
Symmetry codes: (i) −x+3/2, −y+1/2, −z+1; (ii) −x+1, −y, −z+1.
Acknowledgements top

This investigation was supported by NIH/National Cancer Institute grant PO1 CA104457 (to PAC) and by NSF MRI grant CHE 0319176 (to SP).

references
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