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organic compounds
5-Fluoro-1-(4-methoxybenzyl)indoline-2,3-dione
aDepartment of Chemistry, Capital Normal University, Beijing 100048, People's Republic of China
*Correspondence e-mail: sl_cao@sohu.com
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
|
Refinement
|
|
Data collection: APEX2 (Bruker, 2007); cell 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
10.1107/S1600536811023488/sj5156sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536811023488/sj5156Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536811023488/sj5156Isup3.cml
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
on silica gel with dichloromethane as an 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.All the H atoms were discernible in the difference electron density maps. Nevertheless, the hydrogen atoms were placed into idealized positions and allowed to ride on the carrier atoms, with C—H = 0.93 and 0.97 Å for aryl and methylene hydrogens, respectively. Uiso(H) = 1.2Ueq(C)aryl/methylene.
Data collection: APEX2 (Bruker, 2007); cell
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).C16H12FNO3 | Z = 8 |
Mr = 285.27 | F(000) = 1184 |
Orthorhombic, Pbca | Dx = 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 |
Bruker APEXII CCD area-detector diffractometer | 3202 independent reflections |
Radiation source: fine-focus sealed tube | 1604 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.100 |
ω scans | θmax = 27.9°, θmin = 6.4° |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | h = −23→23 |
Tmin = 0.641, Tmax = 0.746 | k = −9→9 |
25325 measured reflections | l = −28→27 |
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(Fo2) + (0.0557P)2 + 0.1083P] where P = (Fo2 + 2Fc2)/3 |
3202 reflections | (Δ/σ)max < 0.001 |
190 parameters | Δρmax = 0.16 e Å−3 |
0 restraints | Δρmin = −0.15 e Å−3 |
C16H12FNO3 | V = 2711.3 (9) Å3 |
Mr = 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 |
Bruker APEXII CCD area-detector diffractometer | 3202 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | 1604 reflections with I > 2σ(I) |
Tmin = 0.641, Tmax = 0.746 | Rint = 0.100 |
25325 measured reflections |
R[F2 > 2σ(F2)] = 0.049 | 0 restraints |
wR(F2) = 0.136 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.16 e Å−3 |
3202 reflections | Δρmin = −0.15 e Å−3 |
190 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
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* |
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) |
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 |
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 |
Mr | 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) |
Tmin, Tmax | 0.641, 0.746 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 25325, 3202, 1604 |
Rint | 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 |
Δρmax, Δρmin (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).
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
Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison,Wisconsin, USA. Google Scholar
Penthala, R. N., Yerramreddy, R. T., Madadi, R. N. & Crooks, A. P. (2010). Bioorg. Med. Chem. 20, 4468–4471. CrossRef CAS Google Scholar
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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.