Acta Cryst. (2009). E65, o8 [ doi:10.1107/S1600536808040178 ]
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.
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.
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).
Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2008).
![[Figure 1]](./si2132fig1thm.gif)
| 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. |
![[Figure 2]](./si2132fig2thm.gif)
| 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. |
| C13H9FN2O | F(000) = 472 |
| Mr = 228.22 | Dx = 1.421 Mg m−3 |
| Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
| a = 7.6093 (5) Å | Cell parameters from 3595 reflections |
| b = 6.1270 (4) Å | θ = 2.7–25.4° |
| c = 22.8912 (16) Å | µ = 0.10 mm−1 |
| β = 91.390 (1)° | T = 293 K |
| V = 1066.92 (12) Å3 | Plates, orange |
| Z = 4 | 0.35 × 0.24 × 0.08 mm |
| Bruker APEX diffractometer | 2552 independent reflections |
| Radiation source: fine-focus sealed tube | 2167 reflections with I > 2σ(I) |
| graphite | Rint = 0.022 |
| Detector resolution: 83.33 pixels mm-1 | θmax = 28.3°, θmin = 1.8° |
| φ and ω scans | h = −9→9 |
| Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | k = −8→8 |
| Tmin = 0.964, Tmax = 0.992 | l = −29→29 |
| 12282 measured reflections |
| Refinement on F2 | Primary atom site location: structure-invariant direct methods |
| Least-squares matrix: full | Secondary atom site location: difference Fourier map |
| R[F2 > 2σ(F2)] = 0.054 | Hydrogen site location: inferred from neighbouring sites |
| wR(F2) = 0.137 | H-atom parameters constrained |
| S = 1.10 | w = 1/[σ2(Fo2) + (0.0587P)2 + 0.3105P] where P = (Fo2 + 2Fc2)/3 |
| 2552 reflections | (Δ/σ)max < 0.001 |
| 154 parameters | Δρmax = 0.23 e Å−3 |
| 0 restraints | Δρmin = −0.22 e Å−3 |
| C13H9FN2O | V = 1066.92 (12) Å3 |
| Mr = 228.22 | Z = 4 |
| Monoclinic, P21/c | Mo Kα radiation |
| a = 7.6093 (5) Å | µ = 0.10 mm−1 |
| b = 6.1270 (4) Å | T = 293 K |
| c = 22.8912 (16) Å | 0.35 × 0.24 × 0.08 mm |
| β = 91.390 (1)° |
| Bruker APEX diffractometer | 2552 independent reflections |
| Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 2167 reflections with I > 2σ(I) |
| Tmin = 0.964, Tmax = 0.992 | Rint = 0.022 |
| 12282 measured reflections | θmax = 28.3° |
| R[F2 > 2σ(F2)] = 0.054 | H-atom parameters constrained |
| wR(F2) = 0.137 | Δρmax = 0.23 e Å−3 |
| S = 1.10 | Δρmin = −0.22 e Å−3 |
| 2552 reflections | Absolute structure: ? |
| 154 parameters | Flack parameter: ? |
| 0 restraints | Rogers parameter: ? |
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. |
| x | y | z | Uiso*/Ueq | ||
| N1 | 0.36941 (18) | 0.7704 (2) | −0.02026 (6) | 0.0462 (3) | |
| H1 | 0.4156 | 0.8783 | −0.0384 | 0.055* | |
| C2 | 0.3608 (2) | 0.7558 (3) | 0.03865 (7) | 0.0422 (4) | |
| O2 | 0.41973 (16) | 0.89761 (19) | 0.07266 (5) | 0.0515 (3) | |
| C3 | 0.27094 (19) | 0.5468 (2) | 0.05187 (7) | 0.0395 (3) | |
| C4 | 0.1488 (2) | 0.2559 (3) | −0.02156 (7) | 0.0457 (4) | |
| H4 | 0.1059 | 0.1591 | 0.0060 | 0.055* | |
| C5 | 0.1325 (2) | 0.2144 (3) | −0.08055 (8) | 0.0503 (4) | |
| F5 | 0.04936 (17) | 0.0275 (2) | −0.09798 (5) | 0.0727 (4) | |
| C6 | 0.1934 (2) | 0.3515 (3) | −0.12313 (7) | 0.0536 (4) | |
| H6 | 0.1788 | 0.3157 | −0.1624 | 0.064* | |
| C7 | 0.2772 (2) | 0.5443 (3) | −0.10659 (7) | 0.0511 (4) | |
| H7 | 0.3204 | 0.6399 | −0.1343 | 0.061* | |
| C8 | 0.2942 (2) | 0.5888 (3) | −0.04789 (7) | 0.0421 (4) | |
| C9 | 0.23179 (19) | 0.4481 (2) | −0.00504 (6) | 0.0395 (3) | |
| C10 | 0.2305 (2) | 0.4604 (3) | 0.10429 (7) | 0.0448 (4) | |
| H10 | 0.1771 | 0.3241 | 0.1019 | 0.054* | |
| N11 | 0.3347 (2) | 0.7320 (3) | 0.17745 (6) | 0.0587 (4) | |
| H11 | 0.3819 | 0.8215 | 0.1535 | 0.070* | |
| C12 | 0.2548 (2) | 0.5398 (3) | 0.16222 (7) | 0.0488 (4) | |
| C13 | 0.1974 (3) | 0.4470 (4) | 0.21346 (8) | 0.0667 (6) | |
| H13 | 0.1390 | 0.3144 | 0.2167 | 0.080* | |
| C14 | 0.2423 (4) | 0.5862 (4) | 0.25906 (9) | 0.0792 (7) | |
| H14 | 0.2184 | 0.5654 | 0.2983 | 0.095* | |
| C15 | 0.3282 (4) | 0.7598 (4) | 0.23562 (9) | 0.0756 (7) | |
| H15 | 0.3746 | 0.8777 | 0.2564 | 0.091* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0597 (8) | 0.0390 (7) | 0.0402 (7) | −0.0043 (6) | 0.0079 (6) | 0.0063 (5) |
| C2 | 0.0462 (8) | 0.0393 (8) | 0.0414 (8) | 0.0013 (6) | 0.0063 (6) | 0.0043 (6) |
| O2 | 0.0673 (8) | 0.0445 (6) | 0.0431 (6) | −0.0124 (5) | 0.0075 (5) | −0.0007 (5) |
| C3 | 0.0408 (7) | 0.0384 (8) | 0.0395 (8) | 0.0016 (6) | 0.0050 (6) | 0.0011 (6) |
| C4 | 0.0496 (9) | 0.0423 (9) | 0.0453 (9) | −0.0009 (7) | 0.0042 (7) | 0.0017 (7) |
| C5 | 0.0562 (10) | 0.0442 (9) | 0.0505 (10) | 0.0006 (7) | −0.0014 (7) | −0.0068 (7) |
| F5 | 0.0964 (9) | 0.0608 (7) | 0.0608 (7) | −0.0194 (6) | −0.0027 (6) | −0.0137 (6) |
| C6 | 0.0669 (11) | 0.0565 (10) | 0.0374 (8) | 0.0071 (9) | −0.0002 (7) | −0.0055 (7) |
| C7 | 0.0663 (11) | 0.0503 (10) | 0.0370 (8) | 0.0057 (8) | 0.0066 (7) | 0.0063 (7) |
| C8 | 0.0465 (8) | 0.0390 (8) | 0.0409 (8) | 0.0055 (6) | 0.0036 (6) | 0.0038 (6) |
| C9 | 0.0411 (7) | 0.0401 (8) | 0.0374 (8) | 0.0053 (6) | 0.0047 (6) | 0.0027 (6) |
| C10 | 0.0473 (8) | 0.0448 (9) | 0.0425 (9) | −0.0051 (7) | 0.0041 (6) | 0.0037 (7) |
| N11 | 0.0806 (11) | 0.0554 (9) | 0.0404 (8) | −0.0147 (8) | 0.0106 (7) | 0.0001 (6) |
| C12 | 0.0545 (9) | 0.0523 (10) | 0.0398 (9) | −0.0033 (7) | 0.0046 (7) | 0.0045 (7) |
| C13 | 0.0903 (15) | 0.0664 (13) | 0.0436 (10) | −0.0170 (11) | 0.0087 (9) | 0.0076 (9) |
| C14 | 0.124 (2) | 0.0762 (15) | 0.0380 (10) | −0.0175 (14) | 0.0131 (11) | 0.0031 (9) |
| C15 | 0.1179 (18) | 0.0673 (13) | 0.0420 (10) | −0.0167 (13) | 0.0082 (11) | −0.0050 (9) |
| N1—C2 | 1.355 (2) | C7—C8 | 1.374 (2) |
| N1—C8 | 1.396 (2) | C7—H7 | 0.9300 |
| N1—H1 | 0.8600 | C8—C9 | 1.397 (2) |
| C2—O2 | 1.2429 (19) | C10—C12 | 1.421 (2) |
| C2—C3 | 1.486 (2) | C10—H10 | 0.9300 |
| C3—C10 | 1.354 (2) | N11—C15 | 1.344 (2) |
| C3—C9 | 1.460 (2) | N11—C12 | 1.367 (2) |
| C4—C5 | 1.377 (2) | N11—H11 | 0.8600 |
| C4—C9 | 1.385 (2) | C12—C13 | 1.384 (2) |
| C4—H4 | 0.9300 | C13—C14 | 1.385 (3) |
| C5—F5 | 1.364 (2) | C13—H13 | 0.9300 |
| C5—C6 | 1.376 (3) | C14—C15 | 1.365 (3) |
| C6—C7 | 1.390 (3) | C14—H14 | 0.9300 |
| C6—H6 | 0.9300 | C15—H15 | 0.9300 |
| C2—N1—C8 | 111.66 (13) | N1—C8—C9 | 108.45 (14) |
| C2—N1—H1 | 124.2 | C4—C9—C8 | 119.57 (14) |
| C8—N1—H1 | 124.2 | C4—C9—C3 | 132.66 (14) |
| O2—C2—N1 | 123.50 (14) | C8—C9—C3 | 107.77 (14) |
| O2—C2—C3 | 129.46 (14) | C3—C10—C12 | 131.79 (16) |
| N1—C2—C3 | 107.04 (14) | C3—C10—H10 | 114.1 |
| C10—C3—C9 | 125.66 (15) | C12—C10—H10 | 114.1 |
| C10—C3—C2 | 129.26 (15) | C15—N11—C12 | 109.57 (16) |
| C9—C3—C2 | 105.08 (13) | C15—N11—H11 | 125.2 |
| C5—C4—C9 | 117.01 (15) | C12—N11—H11 | 125.2 |
| C5—C4—H4 | 121.5 | N11—C12—C13 | 106.60 (16) |
| C9—C4—H4 | 121.5 | N11—C12—C10 | 125.47 (15) |
| F5—C5—C6 | 117.86 (15) | C13—C12—C10 | 127.88 (17) |
| F5—C5—C4 | 118.16 (16) | C12—C13—C14 | 107.97 (19) |
| C6—C5—C4 | 123.97 (16) | C12—C13—H13 | 126.0 |
| C5—C6—C7 | 119.06 (15) | C14—C13—H13 | 126.0 |
| C5—C6—H6 | 120.5 | C15—C14—C13 | 107.19 (18) |
| C7—C6—H6 | 120.5 | C15—C14—H14 | 126.4 |
| C8—C7—C6 | 117.81 (15) | C13—C14—H14 | 126.4 |
| C8—C7—H7 | 121.1 | N11—C15—C14 | 108.66 (19) |
| C6—C7—H7 | 121.1 | N11—C15—H15 | 125.7 |
| C7—C8—N1 | 128.97 (15) | C14—C15—H15 | 125.7 |
| C7—C8—C9 | 122.58 (15) |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O2i | 0.86 | 2.03 | 2.8711 (17) | 166 |
| N11—H11···O2 | 0.86 | 1.94 | 2.6977 (19) | 147 |
| Symmetry codes: (i) −x+1, −y+2, −z. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O2i | 0.86 | 2.03 | 2.8711 (17) | 166 |
| N11—H11···O2 | 0.86 | 1.94 | 2.6977 (19) | 147 |
| Symmetry codes: (i) −x+1, −y+2, −z. |
The authors are grateful for grants from the Welch Foundation (grant No. N-118) and the DARPA (grant No. HR0011–06–1–0032).
Ali, H. M., Laila, M., Rizal, M. R. & Ng, S. W. (2008). Acta Cryst. E64, o921.
Andreani, A., Burnelli, S., Granaiola, M., Leoni, A., Locatelli, A., Morigi, R., Rambaldi, M., Varoli, L. & Kunkel, M. W. (2006). J. Med. Chem. 49, 6922–6924.
Balderamos, M., Ankati, H., Akubathini, S. K., Patel, A. V., Kamila, S., Mukherjee, C., Wang, L., Biehl, E. & D'Mello, S. (2008). Exp. Biol. Med. 233, 1395–1402.
Bruker (1997). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
De, A. (2008). Acta Cryst. E64, o562.
Johnson, K., Liu, L., Majdzadeh, N., Chavez, C., Chin, P. C., Morrison, B., Wang, L., Park, J., Chugh, P., Chen, H. & D'Mello, S. R. (2005). J. Neurochem. 93, 538–548.
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Sun, L., et al. (2003). J. Med. Chem. 46, 1116–1119.
Westrip, S. P. (2008). publCIF. In preparation.
Zhang, H., Ankati, H., Akubathini, S. K. & Biehl, E. (2008). Acta Cryst. E64, o2103.
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).