5-Fluoro-1-(4-meth­oxy­benz­yl)indoline-2,3-dione

Wu, W.; Lin, H.; Wan, C.-Q.; Cao, S.-L.

doi:10.1107/S1600536811023488

organic compounds

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Volume 67| Part 7| July 2011| Page o1834

doi:10.1107/S1600536811023488

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5-Fluoro-1-(4-methoxybenzyl)indoline-2,3-dione

Weiyao Wu,^a Huihui Lin,^a Chong-Qing Wan ^a and Sheng-Li Cao ^a ^*

^aDepartment of Chemistry, Capital Normal University, Beijing 100048, People's Republic of China
^*Correspondence e-mail: sl_cao@sohu.com

(Received 30 May 2011; accepted 16 June 2011; online 30 June 2011)

In the title compound, C₁₆H₁₂FNO₃, the dihedral angle between the benzene ring and the plane of the indole ring system is 71.60 (6)°. In the crystal, molecules stack along the b axis through π–π interactions between the adjacent indole-2,3-dione units with a centroid–centroid distance of 3.649 (3) Å. Intermolecular C—H⋯O=C and C—H⋯π interactions further stabilize the structure, forming a three-dimensional framework.

Related literature

For background to the use of 5-fluoroindoline-2,3-dione and its analogues as anti-tumour agents, see: Uddin et al. (2007 ); Penthala et al. (2010 ). For a related structure, see: Wu et al. (2011 ).

Experimental

Crystal data

C₁₆H₁₂FNO₃
M_r = 285.27
Orthorhombic, P b c a
a = 17.779 (4) Å
b = 7.1575 (14) Å
c = 21.306 (4) Å
V = 2711.3 (9) Å³
Z = 8
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 296 K
0.40 × 0.30 × 0.20 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2007 ) T_min = 0.641, T_max = 0.746
25325 measured reflections
3202 independent reflections
1604 reflections with I > 2σ(I)
R_int = 0.100

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.136
S = 1.01
3202 reflections
190 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C1–C6 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15A⋯Cg1ⁱ	0.93	3.03	3.812 (2)	142
C14—H14A⋯O2ⁱⁱ	0.93	2.49	3.345 (2)	153
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ ; (ii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ .

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 and SAINT (Bruker, 2007); 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 PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811023488/sj5156sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811023488/sj5156Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811023488/sj5156Isup3.cml

checkCIF report

Comment top

The derivatives of 5-fluoroindoline-2,3-dione and its analogues are widely used as anti-tumor compounds (Uddin et al., 2007; Penthala et al., 2010). Herein, we report the crystal structure of one new derivative of 5-fluoroindoline-2,3-dione.

In the title compound C₁₆H₁₂FNO₃, the indoline moiety links to the 4-methoxybenzene through methylene group with a C5-C7(methylene)-N1 angle of 113.29 (2)° (Fig. 1). The benzene ring and the plane of the indole-2,3-dione exhibit a dihedral angle of 71.60 (6)°. The C5-C7(methylene)-N1 angle and the dihedral angle are comparable to these in the chloro-substituted compound, 5-chloro-1- (4-methoxybenzyl)indoline-2,3-dione, where the corresponding values are 113.86 (2)° and 88.44 (8)° (Wu et al. 2011). Molecules stack along the b axis through π–π stacking interactions between adjacent indole-2,3-dione units with a Cg···Cg distance of 3.649 (3)Å and C15-H15A···Cg contacts, Table 1, form a chain structure, as shown in Fig. 2. The almost parallel chains are further interconnected through C14-H14A···O2═C9 interactions, Table 1, generating a three-dimensional framework, Fig. 2.

Related literature top

For background to the use of 5-fluoroindoline-2,3-dione and its analogues as anti-tumour agents, see: Uddin et al. (2007); Penthala et al. (2010). For a related structure, see: Wu et al. (2011).

Experimental top

To an ice-bath cooled solution of 5-fluoroindoline-2,3-dione (0.33 g, 2 mmol) in N,N-dimethylformamide (20 ml) was added potassium carbonate (0.33 g, 2.4 mmol) and potassium iodide (0.07 g, 0.4 mmol) followed by 4-methoxybenzyl chloride (0.32 ml, 2.2 mmol). The reaction mixture was stirred at 110 °C for 3 h. After cooling to room temperature, the reaction mixture was poured into ice water (80 ml). The resulting precipitate was filtered and subsequently purified by column chromatography on silica gel with dichloromethane as an eluent to give the title compound (Rf = 0.81, dichloromethane; m.p. 138-139 °C; yield 78%). Yellow crystals of the title compound were obtained by slow evaporation from the solution of dichloromethane/ethanol 8:2 (v/v) at room temperature after a week.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 and SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); 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 PLATON (Spek, 2009).

Figures top

	Fig. 1. The title molecule with the atomic numbering scheme. The displacement ellipsoids are shown at the 30% probability level, while the hydrogen atoms are shown as spheres of arbitrary radius.
	Fig. 2. View down the b axis of the crystal packing of the title compound.

5-Fluoro-1-(4-methoxybenzyl)indoline-2,3-dione top

Crystal data top

C₁₆H₁₂FNO₃	Z = 8
M_r = 285.27	F(000) = 1184
Orthorhombic, Pbca	D_x = 1.398 Mg m⁻³
Hall symbol: -P 2ac 2ab	Mo Kα radiation, λ = 0.71073 Å
a = 17.779 (4) Å	µ = 0.11 mm⁻¹
b = 7.1575 (14) Å	T = 296 K
c = 21.306 (4) Å	Block, yellow
V = 2711.3 (9) Å³	0.40 × 0.30 × 0.20 mm

Data collection top

Bruker APEXII CCD area-detector diffractometer	3202 independent reflections
Radiation source: fine-focus sealed tube	1604 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.100
ω scans	θ_max = 27.9°, θ_min = 6.4°
Absorption correction: multi-scan (SADABS; Bruker, 2007)	h = −23→23
T_min = 0.641, T_max = 0.746	k = −9→9
25325 measured reflections	l = −28→27

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.136	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.0557P)² + 0.1083P] where P = (F_o² + 2F_c²)/3
3202 reflections	(Δ/σ)_max < 0.001
190 parameters	Δρ_max = 0.16 e Å⁻³
0 restraints	Δρ_min = −0.15 e Å⁻³

Crystal data top

C₁₆H₁₂FNO₃	V = 2711.3 (9) Å³
M_r = 285.27	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 17.779 (4) Å	µ = 0.11 mm⁻¹
b = 7.1575 (14) Å	T = 296 K
c = 21.306 (4) Å	0.40 × 0.30 × 0.20 mm

Data collection top

Bruker APEXII CCD area-detector diffractometer	3202 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2007)	1604 reflections with I > 2σ(I)
T_min = 0.641, T_max = 0.746	R_int = 0.100
25325 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.136	H-atom parameters constrained
S = 1.01	Δρ_max = 0.16 e Å⁻³
3202 reflections	Δρ_min = −0.15 e Å⁻³
190 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
F1	0.08487 (7)	0.2819 (2)	0.39404 (6)	0.0874 (4)
O1	0.38817 (8)	0.2815 (2)	0.34962 (7)	0.0788 (5)
O2	0.47658 (8)	0.2065 (2)	0.46416 (7)	0.0738 (5)
O3	0.36524 (10)	0.7189 (2)	0.74362 (7)	0.0833 (5)
N1	0.35821 (8)	0.1683 (2)	0.50669 (7)	0.0508 (4)
C1	0.42398 (10)	0.5766 (3)	0.65265 (9)	0.0569 (5)
H1A	0.4579	0.6745	0.6482	0.068*
C2	0.37197 (11)	0.5783 (3)	0.70053 (9)	0.0579 (5)
C3	0.32168 (12)	0.4322 (3)	0.70640 (9)	0.0668 (6)
H3A	0.2866	0.4325	0.7388	0.080*
C4	0.32346 (12)	0.2861 (3)	0.66446 (10)	0.0630 (6)
H4A	0.2890	0.1892	0.6687	0.076*
C5	0.37553 (11)	0.2802 (3)	0.61599 (8)	0.0502 (5)
C6	0.42526 (10)	0.4275 (3)	0.61115 (9)	0.0542 (5)
H6A	0.4607	0.4268	0.5791	0.065*
C7	0.37914 (11)	0.1181 (3)	0.57101 (9)	0.0576 (5)
H7A	0.4299	0.0683	0.5709	0.069*
H7B	0.3458	0.0202	0.5857	0.069*
C8	0.36179 (12)	0.2478 (3)	0.40047 (10)	0.0543 (5)
C9	0.40834 (11)	0.2057 (3)	0.45996 (9)	0.0545 (5)
C10	0.28347 (10)	0.1884 (2)	0.48441 (9)	0.0451 (4)
C11	0.28318 (10)	0.2373 (2)	0.42095 (9)	0.0472 (5)
C12	0.21641 (11)	0.2671 (3)	0.38876 (9)	0.0552 (5)
H12A	0.2157	0.2987	0.3464	0.066*
C13	0.15144 (11)	0.2476 (3)	0.42286 (10)	0.0570 (5)
C14	0.15047 (11)	0.1975 (3)	0.48525 (10)	0.0569 (5)
H14A	0.1048	0.1840	0.5060	0.068*
C15	0.21751 (10)	0.1671 (3)	0.51749 (9)	0.0522 (5)
H15A	0.2177	0.1337	0.5597	0.063*
C16	0.42269 (18)	0.8594 (4)	0.74439 (13)	0.0992 (9)
H16A	0.4116	0.9495	0.7764	0.149*
H16B	0.4245	0.9205	0.7043	0.149*
H16C	0.4704	0.8021	0.7529	0.149*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0514 (7)	0.1155 (11)	0.0953 (10)	0.0063 (7)	−0.0130 (6)	0.0019 (8)
O1	0.0704 (10)	0.1040 (13)	0.0619 (10)	−0.0115 (8)	0.0144 (8)	0.0097 (8)
O2	0.0460 (9)	0.0904 (11)	0.0851 (11)	−0.0052 (7)	0.0015 (7)	0.0017 (8)
O3	0.0923 (12)	0.0894 (12)	0.0682 (10)	−0.0015 (9)	0.0081 (8)	−0.0262 (9)
N1	0.0480 (9)	0.0532 (9)	0.0510 (9)	−0.0020 (7)	−0.0001 (7)	−0.0018 (7)
C1	0.0512 (11)	0.0608 (13)	0.0587 (12)	−0.0066 (9)	−0.0012 (9)	−0.0035 (10)
C2	0.0604 (12)	0.0652 (13)	0.0480 (11)	0.0062 (11)	−0.0031 (10)	−0.0060 (10)
C3	0.0643 (13)	0.0856 (17)	0.0504 (12)	−0.0053 (12)	0.0107 (10)	−0.0008 (11)
C4	0.0614 (13)	0.0679 (14)	0.0597 (13)	−0.0122 (10)	0.0016 (10)	0.0056 (11)
C5	0.0499 (11)	0.0530 (12)	0.0479 (11)	0.0043 (9)	−0.0050 (9)	0.0054 (9)
C6	0.0448 (11)	0.0656 (13)	0.0520 (11)	0.0007 (10)	0.0024 (8)	−0.0009 (10)
C7	0.0609 (12)	0.0558 (12)	0.0560 (12)	0.0012 (9)	−0.0057 (10)	0.0028 (10)
C8	0.0558 (12)	0.0522 (12)	0.0549 (12)	−0.0070 (9)	0.0042 (10)	0.0004 (9)
C9	0.0483 (12)	0.0524 (12)	0.0628 (13)	−0.0044 (9)	0.0039 (10)	−0.0036 (9)
C10	0.0448 (10)	0.0388 (10)	0.0516 (11)	−0.0020 (8)	0.0028 (8)	−0.0063 (8)
C11	0.0472 (11)	0.0432 (10)	0.0513 (11)	−0.0031 (8)	0.0022 (8)	−0.0030 (8)
C12	0.0584 (13)	0.0533 (12)	0.0539 (12)	−0.0027 (9)	−0.0025 (9)	0.0002 (9)
C13	0.0448 (11)	0.0568 (12)	0.0694 (14)	−0.0004 (9)	−0.0068 (10)	−0.0036 (10)
C14	0.0466 (11)	0.0541 (12)	0.0699 (14)	−0.0051 (9)	0.0086 (9)	−0.0061 (10)
C15	0.0542 (12)	0.0488 (11)	0.0536 (11)	−0.0029 (9)	0.0079 (9)	−0.0027 (9)
C16	0.138 (3)	0.0752 (17)	0.0848 (18)	−0.0146 (18)	−0.0027 (16)	−0.0240 (14)

Geometric parameters (Å, º) top

F1—C13	1.356 (2)	C6—H6A	0.9300
O1—C8	1.205 (2)	C7—H7A	0.9700
O2—C9	1.217 (2)	C7—H7B	0.9700
O3—C2	1.368 (2)	C8—C11	1.466 (3)
O3—C16	1.433 (3)	C8—C9	1.544 (3)
N1—C9	1.363 (2)	C10—C15	1.377 (2)
N1—C10	1.418 (2)	C10—C11	1.396 (3)
N1—C7	1.465 (2)	C11—C12	1.388 (3)
C1—C2	1.377 (3)	C12—C13	1.372 (3)
C1—C6	1.386 (3)	C12—H12A	0.9300
C1—H1A	0.9300	C13—C14	1.377 (3)
C2—C3	1.382 (3)	C14—C15	1.393 (3)
C3—C4	1.375 (3)	C14—H14A	0.9300
C3—H3A	0.9300	C15—H15A	0.9300
C4—C5	1.388 (3)	C16—H16A	0.9600
C4—H4A	0.9300	C16—H16B	0.9600
C5—C6	1.380 (3)	C16—H16C	0.9600
C5—C7	1.507 (3)

C2—O3—C16	117.50 (18)	O1—C8—C9	124.66 (19)
C9—N1—C10	110.37 (15)	C11—C8—C9	104.88 (16)
C9—N1—C7	124.44 (16)	O2—C9—N1	126.83 (19)
C10—N1—C7	125.18 (15)	O2—C9—C8	126.46 (18)
C2—C1—C6	119.38 (18)	N1—C9—C8	106.71 (16)
C2—C1—H1A	120.3	C15—C10—C11	121.35 (17)
C6—C1—H1A	120.3	C15—C10—N1	127.97 (17)
O3—C2—C1	124.24 (19)	C11—C10—N1	110.67 (15)
O3—C2—C3	116.10 (18)	C12—C11—C10	121.35 (16)
C1—C2—C3	119.66 (18)	C12—C11—C8	131.34 (17)
C4—C3—C2	120.11 (19)	C10—C11—C8	107.31 (16)
C4—C3—H3A	119.9	C13—C12—C11	116.29 (18)
C2—C3—H3A	119.9	C13—C12—H12A	121.9
C3—C4—C5	121.47 (19)	C11—C12—H12A	121.9
C3—C4—H4A	119.3	F1—C13—C12	118.47 (19)
C5—C4—H4A	119.3	F1—C13—C14	118.25 (18)
C6—C5—C4	117.37 (18)	C12—C13—C14	123.27 (18)
C6—C5—C7	120.92 (17)	C13—C14—C15	120.39 (18)
C4—C5—C7	121.70 (18)	C13—C14—H14A	119.8
C5—C6—C1	122.01 (17)	C15—C14—H14A	119.8
C5—C6—H6A	119.0	C10—C15—C14	117.34 (18)
C1—C6—H6A	119.0	C10—C15—H15A	121.3
N1—C7—C5	113.29 (15)	C14—C15—H15A	121.3
N1—C7—H7A	108.9	O3—C16—H16A	109.5
C5—C7—H7A	108.9	O3—C16—H16B	109.5
N1—C7—H7B	108.9	H16A—C16—H16B	109.5
C5—C7—H7B	108.9	O3—C16—H16C	109.5
H7A—C7—H7B	107.7	H16A—C16—H16C	109.5
O1—C8—C11	130.47 (19)	H16B—C16—H16C	109.5

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the C1–C6 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···Cg1ⁱ	0.93	3.03	3.812 (2)	142
C14—H14A···O2ⁱⁱ	0.93	2.49	3.345 (2)	153

Symmetry codes: (i) −x+1/2, y−1/2, z; (ii) x−1/2, −y+1/2, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₂FNO₃
M_r	285.27
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	296
a, b, c (Å)	17.779 (4), 7.1575 (14), 21.306 (4)
V (Å³)	2711.3 (9)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.40 × 0.30 × 0.20

Data collection
Diffractometer	Bruker APEXII CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2007)
T_min, T_max	0.641, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	25325, 3202, 1604
R_int	0.100
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.136, 1.01
No. of reflections	3202
No. of parameters	190
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.16, −0.15

Computer programs: APEX2 (Bruker, 2007), APEX2 and SAINT (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the C1–C6 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···Cg1ⁱ	0.93	3.03	3.812 (2)	142
C14—H14A···O2ⁱⁱ	0.93	2.49	3.345 (2)	153

Symmetry codes: (i) −x+1/2, y−1/2, z; (ii) x−1/2, −y+1/2, −z+1.

Acknowledgements

The authors are grateful to the National Science Foundation Committee (project No. 20972099) for financial support.

References

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