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Acta Crystallogr Sect E Struct Rep Online. 2009 January 1; 65(Pt 1): o8.
Published online 2008 December 3. doi:  10.1107/S1600536808040178
PMCID: PMC2967860

(Z)-5-Fluoro-3-[(1H-pyrrol-2-yl)methyl­ene]indolin-2-one

Abstract

The title compound, C13H9FN2O, a potential neuroprotective agent, consists of an indolinone and a pyrrolyl unit [dihedral angle between the ring planes = 4.9 (1)°]. An intra­molecular hydrogen bond between the carbonyl O atom and the NH group of pyrrole correlates with the Z arrangement of the substituents at the C=C bond. In the crystal, inversion dimers occur, linked by pairs of N—H(...)O bonds.

Related literature

For 3-substituted indole-2-one derivatives tested as protein kinase inhibitors, see: Sun et al. (2003 [triangle]). For derivatives with anti­tumor activity, see: Andreani et al. (2006 [triangle]). For derivatives with neuroprotective properties, see: Balderamos et al. (2008 [triangle]); Johnson et al. (2005 [triangle]). For related structures, see: Ali et al. (2008 [triangle]); De (2008 [triangle]); Zhang et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-000o8-scheme1.jpg

Experimental

Crystal data

  • C13H9FN2O
  • M r = 228.22
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-000o8-efi1.jpg
  • a = 7.6093 (5) Å
  • b = 6.1270 (4) Å
  • c = 22.8912 (16) Å
  • β = 91.390 (1)°
  • V = 1066.92 (12) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 (2) K
  • 0.35 × 0.24 × 0.08 mm

Data collection

  • Bruker APEX diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.964, T max = 0.992
  • 12282 measured reflections
  • 2552 independent reflections
  • 2167 reflections with I > 2σ(I)
  • R int = 0.022

Refinement

  • R[F 2 > 2σ(F 2)] = 0.054
  • wR(F 2) = 0.137
  • S = 1.10
  • 2552 reflections
  • 154 parameters
  • H-atom parameters constrained
  • Δρmax = 0.23 e Å−3
  • Δρmin = −0.22 e Å−3

Data collection: SMART (Bruker, 1997 [triangle]); cell refinement: SAINT (Bruker, 1997 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL and publCIF (Westrip, 2008 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808040178/si2132sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808040178/si2132Isup2.hkl

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

Acknowledgments

The authors are grateful for grants from the Welch Foundation (grant No. N-118) and the DARPA (grant No. HR0011-06-1-0032).

supplementary crystallographic information

Comment

3-Substituted indoline-2-ones are a variety of pharmacologically important compounds such as protein kinase inhibitors (Sun et al., 2003), antitumor (Andreani et al., 2006) and neuroprotective properties (Balderamos et al., 2008; Johnson et al., 2005). We have designed, synthesized and crystallized several 3-substituted indoline-2-one derivatives to study their neuroprotective properties. In order to study on the relationship between the activity of 3-substituted indoline-2-ones and the importance of halogenated substituent at the 5-postion, the fluoro derivative was synthesized and its crystal structure is reported here. An intramolecular hydrogen bond was found between the N—H of pyrrole and the carbonyl O and a hepta cyclic membered ring was formed (Table 1) (Fig 1). Unlike the E arrangement of the chloro derivative (Zhang, et al., 2008), thanks to the intramolecular H bond, the title compound adopted a Z conformation (Fig 1). Compared to the bond length C – Cl 1.736 (5) Å, the C – F is 1.364 (2) Å in the current structure, similar to other indolin-2-one compounds (Ali, et al., 2008; De, 2008; Zhang, et al., 2008;) which contain intermolecular N—H···O hydrogen bonds. The H-bonds link two inverted molecules, forming an octa cyclic membered ring, and a dimer is constructed (Table 1) (Fig 2).

Experimental

The title compound was synthesized by the condensation of pyrrole-2-carboxaldehyde (1 mmol) with 5-fluoro-oxindole (1 mmol) in ethanol (10 ml) in the presence of catalytic amount of piperidine (0.1 mmol). After refluxing for 3 hr, the reaction mixture was left to stand for overnight. The resulting crude solid was filtered, washed with cold ethanol (10 ml) and dried. Orange red single crystals of the compound suitable for x-ray structure determination were recrystallized from ethanol.

Refinement

All H atom were placed in calculated positions and included in the final cycles of refinement using a riding model, with distances N–H = 0.86 Å and C–H = 0.93 Å, and displacement parameters Uiso(H) = 1.2Ueq(N,C).

Figures

Fig. 1.
: A view of one of the independent molecules with displacement ellipsoids drawn at the 40% probability level. Dash lines indicate the intramolecular hydrogen bond. H atoms are presented as open circles with arbitrary radii.
Fig. 2.
: A unit cell packing view of the title compound. Dash lines indicate the intra- and intermolecular hydrogen bonds. H atoms are presented as open circles with arbitrary radii.

Crystal data

C13H9FN2OF(000) = 472
Mr = 228.22Dx = 1.421 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 7.6093 (5) ÅCell parameters from 3595 reflections
b = 6.1270 (4) Åθ = 2.7–25.4°
c = 22.8912 (16) ŵ = 0.10 mm1
β = 91.390 (1)°T = 293 K
V = 1066.92 (12) Å3Plates, orange
Z = 40.35 × 0.24 × 0.08 mm

Data collection

Bruker APEX diffractometer2552 independent reflections
Radiation source: fine-focus sealed tube2167 reflections with I > 2σ(I)
graphiteRint = 0.022
Detector resolution: 83.33 pixels mm-1θmax = 28.3°, θmin = 1.8°
[var phi] and ω scansh = −9→9
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)k = −8→8
Tmin = 0.964, Tmax = 0.992l = −29→29
12282 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.054Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H-atom parameters constrained
S = 1.10w = 1/[σ2(Fo2) + (0.0587P)2 + 0.3105P] where P = (Fo2 + 2Fc2)/3
2552 reflections(Δ/σ)max < 0.001
154 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = −0.22 e Å3

Special details

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 > σ(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)

xyzUiso*/Ueq
N10.36941 (18)0.7704 (2)−0.02026 (6)0.0462 (3)
H10.41560.8783−0.03840.055*
C20.3608 (2)0.7558 (3)0.03865 (7)0.0422 (4)
O20.41973 (16)0.89761 (19)0.07266 (5)0.0515 (3)
C30.27094 (19)0.5468 (2)0.05187 (7)0.0395 (3)
C40.1488 (2)0.2559 (3)−0.02156 (7)0.0457 (4)
H40.10590.15910.00600.055*
C50.1325 (2)0.2144 (3)−0.08055 (8)0.0503 (4)
F50.04936 (17)0.0275 (2)−0.09798 (5)0.0727 (4)
C60.1934 (2)0.3515 (3)−0.12313 (7)0.0536 (4)
H60.17880.3157−0.16240.064*
C70.2772 (2)0.5443 (3)−0.10659 (7)0.0511 (4)
H70.32040.6399−0.13430.061*
C80.2942 (2)0.5888 (3)−0.04789 (7)0.0421 (4)
C90.23179 (19)0.4481 (2)−0.00504 (6)0.0395 (3)
C100.2305 (2)0.4604 (3)0.10429 (7)0.0448 (4)
H100.17710.32410.10190.054*
N110.3347 (2)0.7320 (3)0.17745 (6)0.0587 (4)
H110.38190.82150.15350.070*
C120.2548 (2)0.5398 (3)0.16222 (7)0.0488 (4)
C130.1974 (3)0.4470 (4)0.21346 (8)0.0667 (6)
H130.13900.31440.21670.080*
C140.2423 (4)0.5862 (4)0.25906 (9)0.0792 (7)
H140.21840.56540.29830.095*
C150.3282 (4)0.7598 (4)0.23562 (9)0.0756 (7)
H150.37460.87770.25640.091*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0597 (8)0.0390 (7)0.0402 (7)−0.0043 (6)0.0079 (6)0.0063 (5)
C20.0462 (8)0.0393 (8)0.0414 (8)0.0013 (6)0.0063 (6)0.0043 (6)
O20.0673 (8)0.0445 (6)0.0431 (6)−0.0124 (5)0.0075 (5)−0.0007 (5)
C30.0408 (7)0.0384 (8)0.0395 (8)0.0016 (6)0.0050 (6)0.0011 (6)
C40.0496 (9)0.0423 (9)0.0453 (9)−0.0009 (7)0.0042 (7)0.0017 (7)
C50.0562 (10)0.0442 (9)0.0505 (10)0.0006 (7)−0.0014 (7)−0.0068 (7)
F50.0964 (9)0.0608 (7)0.0608 (7)−0.0194 (6)−0.0027 (6)−0.0137 (6)
C60.0669 (11)0.0565 (10)0.0374 (8)0.0071 (9)−0.0002 (7)−0.0055 (7)
C70.0663 (11)0.0503 (10)0.0370 (8)0.0057 (8)0.0066 (7)0.0063 (7)
C80.0465 (8)0.0390 (8)0.0409 (8)0.0055 (6)0.0036 (6)0.0038 (6)
C90.0411 (7)0.0401 (8)0.0374 (8)0.0053 (6)0.0047 (6)0.0027 (6)
C100.0473 (8)0.0448 (9)0.0425 (9)−0.0051 (7)0.0041 (6)0.0037 (7)
N110.0806 (11)0.0554 (9)0.0404 (8)−0.0147 (8)0.0106 (7)0.0001 (6)
C120.0545 (9)0.0523 (10)0.0398 (9)−0.0033 (7)0.0046 (7)0.0045 (7)
C130.0903 (15)0.0664 (13)0.0436 (10)−0.0170 (11)0.0087 (9)0.0076 (9)
C140.124 (2)0.0762 (15)0.0380 (10)−0.0175 (14)0.0131 (11)0.0031 (9)
C150.1179 (18)0.0673 (13)0.0420 (10)−0.0167 (13)0.0082 (11)−0.0050 (9)

Geometric parameters (Å, °)

N1—C21.355 (2)C7—C81.374 (2)
N1—C81.396 (2)C7—H70.9300
N1—H10.8600C8—C91.397 (2)
C2—O21.2429 (19)C10—C121.421 (2)
C2—C31.486 (2)C10—H100.9300
C3—C101.354 (2)N11—C151.344 (2)
C3—C91.460 (2)N11—C121.367 (2)
C4—C51.377 (2)N11—H110.8600
C4—C91.385 (2)C12—C131.384 (2)
C4—H40.9300C13—C141.385 (3)
C5—F51.364 (2)C13—H130.9300
C5—C61.376 (3)C14—C151.365 (3)
C6—C71.390 (3)C14—H140.9300
C6—H60.9300C15—H150.9300
C2—N1—C8111.66 (13)N1—C8—C9108.45 (14)
C2—N1—H1124.2C4—C9—C8119.57 (14)
C8—N1—H1124.2C4—C9—C3132.66 (14)
O2—C2—N1123.50 (14)C8—C9—C3107.77 (14)
O2—C2—C3129.46 (14)C3—C10—C12131.79 (16)
N1—C2—C3107.04 (14)C3—C10—H10114.1
C10—C3—C9125.66 (15)C12—C10—H10114.1
C10—C3—C2129.26 (15)C15—N11—C12109.57 (16)
C9—C3—C2105.08 (13)C15—N11—H11125.2
C5—C4—C9117.01 (15)C12—N11—H11125.2
C5—C4—H4121.5N11—C12—C13106.60 (16)
C9—C4—H4121.5N11—C12—C10125.47 (15)
F5—C5—C6117.86 (15)C13—C12—C10127.88 (17)
F5—C5—C4118.16 (16)C12—C13—C14107.97 (19)
C6—C5—C4123.97 (16)C12—C13—H13126.0
C5—C6—C7119.06 (15)C14—C13—H13126.0
C5—C6—H6120.5C15—C14—C13107.19 (18)
C7—C6—H6120.5C15—C14—H14126.4
C8—C7—C6117.81 (15)C13—C14—H14126.4
C8—C7—H7121.1N11—C15—C14108.66 (19)
C6—C7—H7121.1N11—C15—H15125.7
C7—C8—N1128.97 (15)C14—C15—H15125.7
C7—C8—C9122.58 (15)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.862.032.8711 (17)166
N11—H11···O20.861.942.6977 (19)147

Symmetry codes: (i) −x+1, −y+2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SI2132).

References

  • Ali, H. M., Laila, M., Rizal, M. R. & Ng, S. W. (2008). Acta Cryst. E64, o921. [PMC free article] [PubMed]
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