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

Zhang, H.; Ankati, H.; Akubathini, S.K.; Biehl, E.

doi:10.1107/S1600536808040178

organic compounds

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Volume 65| Part 1| January 2009| Page o8

doi:10.1107/S1600536808040178

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

Hongming Zhang,^a ^* Haribabu Ankati,^a Shashidhar Kumar Akubathini ^a and Ed Biehl ^a

^aDepartment of Chemistry, Southern Methodist University, Dallas, TX 75275, USA
^*Correspondence e-mail: hzhang@smu.edu

(Received 7 November 2008; accepted 28 November 2008; online 3 December 2008)

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 ). For derivatives with antitumor activity, see: Andreani et al. (2006 ). For derivatives with neuroprotective properties, see: Balderamos et al. (2008 ); Johnson et al. (2005 ). For related structures, see: Ali et al. (2008 ); De (2008 ); Zhang et al. (2008 ).

Experimental

Crystal data

C₁₃H₉FN₂O
M_r = 228.22
Monoclinic, P 2₁ /c
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 ) 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[F² > 2σ(F²)] = 0.054
wR(F²) = 0.137
S = 1.10
2552 reflections
154 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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 code: (i) -x+1, -y+2, -z.

Data collection: SMART (Bruker, 1997 ); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; 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 and publCIF (Westrip, 2008 ).

Supporting information

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

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

checkCIF report

Comment top

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).

Related literature top

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

Experimental top

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.

Computing details top

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).

Figures top

	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.

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

Crystal data top

C₁₃H₉FN₂O	F(000) = 472
M_r = 228.22	D_x = 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

Data collection top

Bruker APEX diffractometer	2552 independent reflections
Radiation source: fine-focus sealed tube	2167 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
Detector resolution: 83.33 pixels mm^-1	θ_max = 28.3°, θ_min = 1.8°
ϕ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −8→8
T_min = 0.964, T_max = 0.992	l = −29→29
12282 measured reflections

Refinement top

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(F_o²) + (0.0587P)² + 0.3105P] where P = (F_o² + 2F_c²)/3
2552 reflections	(Δ/σ)_max < 0.001
154 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₃H₉FN₂O	V = 1066.92 (12) Å³
M_r = 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)°

Data collection top

Bruker APEX diffractometer	2552 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	2167 reflections with I > 2σ(I)
T_min = 0.964, T_max = 0.992	R_int = 0.022
12282 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.054	0 restraints
wR(F²) = 0.137	H-atom parameters constrained
S = 1.10	Δρ_max = 0.23 e Å⁻³
2552 reflections	Δρ_min = −0.22 e Å⁻³
154 parameters

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 > 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) top

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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 code: (i) −x+1, −y+2, −z.

Experimental details

Crystal data
Chemical formula	C₁₃H₉FN₂O
M_r	228.22
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	7.6093 (5), 6.1270 (4), 22.8912 (16)
β (°)	91.390 (1)
V (Å³)	1066.92 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.35 × 0.24 × 0.08

Data collection
Diffractometer	Bruker APEX diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.964, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	12282, 2552, 2167
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.054, 0.137, 1.10
No. of reflections	2552
No. of parameters	154
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.22

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.86	2.03	2.8711 (17)	165.9
N11—H11···O2	0.86	1.94	2.6977 (19)	146.8

Symmetry code: (i) −x+1, −y+2, −z.

Acknowledgements

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

References

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