Methyl 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetate

Wang, S.; Dong, H.; Chen, H.; Zhu, K.; Zhu, T.

doi:10.1107/S1600536809053033

organic compounds

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ISSN: 2056-9890

Volume 66| Part 1| January 2010| Page o155

doi:10.1107/S1600536809053033

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Methyl 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetate

Shuping Wang,^a Huajiang Dong,^a Hong Chen,^a Kunpeng Zhu ^a and Tieliang Zhu ^a ^*

^aThe Affiliated Hospital of the Medical College of the Chinese People's Armed Police Forces, Tianjin 300162, People's Republic of China
^*Correspondence e-mail: shupingwang203@yahoo.com.cn

(Received 2 December 2009; accepted 9 December 2009; online 16 December 2009)

The indolyl portion of the title molecule, C₁₁H₈FNO₃, is flat, the five- and six-membered rings making a dihedral angle of 0.815 (6)°. Intermolecular N—H⋯O hydrogen bonds link adjacent molecules into a linear chain. Slipped π–π stacking interactions between two neighboring indole groups further consolidate the molecules into a three-dimensional supramolecular architecture [centroid–centroid distances = 3.555 (10) and 3.569 (10) Å].

Related literature

For the biological activity of the title compound and its derivatives, see: Kozikowski et al. (2006 ); Albert et al. (2002 ); Jaquith et al. (2005 ). For the preparation, see: Alawar et al. (2004 ).

Experimental

Crystal data

C₁₁H₈FNO₃
M_r = 221.18
Monoclinic, P 2₁ /c
a = 7.0584 (14) Å
b = 20.586 (4) Å
c = 7.3286 (15) Å
β = 112.01 (3)°
V = 987.3 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 113 K
0.30 × 0.24 × 0.20 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2004 ) T_min = 0.964, T_max = 0.976
9472 measured reflections
2328 independent reflections
2097 reflections with I > 2σ(I)
R_int = 0.024

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.097
S = 1.06
2328 reflections
150 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O3ⁱ	0.932 (17)	2.420 (16)	3.1598 (13)	136.3 (13)
N1—H1⋯O1ⁱ	0.932 (17)	1.932 (17)	2.7861 (13)	151.3 (14)
Symmetry code: (i) x, y, z-1.

Data collection: CrystalClear (Rigaku/MSC, 2004); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXL97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 1999 ); software used to prepare material for publication: publCIF (Westrip, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809053033/ng2701sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809053033/ng2701Isup2.hkl

checkCIF report

Comment top

The synthesis of the title compound (I) and its derivatives has received considerable attention on account of their biological activity especially for both enzymic and cell-based study (Kozikowski et al., 2006). They also can be used as neuroprotective (Albert et al., 2002) and anti-proliferative agents (Jaquith et al., 2005).

In this work, the title molecule, C₁₁H₈FNO₃, (Fig. 1), has been synthesized. In an asymmetric unit of (I) one molecule can be observed. (I) crystalizes in the Monoclinic P2(1)/n space group, a = 7.0584 (14) Å, b = 20.586 (4) Å, c = 7.3286 (15) Å, β = 112.01 (3)°. The heterocyclic rings (N1, C1, C6, C7, C8) make a small dihedral angle of 0.815 (6)° with benzene rings (C1, C2, C3, C4, C5, C6,). N atoms in the molecule act as hydrogen-bond donors to O atoms in the neighbouring molecule forming intermolecular N1—H1···O1 (symmetry code: x, y, z - 1) and N1—H1···O3 (symmetry code: x, y, z - 1) hydrogen bonds. These N—H···O hydrogen bonds, C3—H3···F1(symmetry code: x, -y + 1/2, z - 1/2), and intra-molecular C5—H5···O1, C8—H8···O2 hydrogen bonds stabilize the crystal structure and extend molecules (I) into a double-tape structure along the c direction. π–π interactions between the indole rings are also present, the centroid-centroid distances [symmetry code: 1 - x,-y,2 - z; 2 - x,-y,2 - z] are 3.555 (10) and 3.569 (10) Å. N—H···π interactions [symmetry code: 1 - x,-y,2 - z] are 3.218 (21) Å. These Parallel slipped π-π stacking interactions between two neighboring indole groups and N—H···π interactions also further consolidate (I) into the three-dimensional supramolecular architecture.

Perspective drawing with the atomic numbering scheme is illustrated in Figure 1. Selected geometric parameters (Å, °) for (I) are listed in table 1. Selected hydrogen-bonding geometric parameters (Å, °) for (I) are listed in table 2. The corresponding N—H···O, C—H···O and C—H···F hydrogen bonds are shown in Figure 2. The π-π stacking interactions and N—H···π interactions are shown in Ffigure 3. The three-dimensional supramolecular packing architecture of (I) is shown in Figure 4.

Related literature top

For the biological activity of the title compound and its derivatives, see: Kozikowski et al. (2006); Albert et al. (2002); Jaquith et al. (2005). For the preparation, see: Alawar et al. (2004).

Experimental top

Methyl 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetate was prepared according to the previous literature (Alawar et al., 2004). Colorless block Single crystals were obtained by slow evaporation from a methanol and water mixed solution (150 ml) of (I) at room temperature.

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2004); cell refinement: CrystalClear (Rigaku/MSC, 2004); data reduction: CrystalClear (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXL97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 1999); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures top

	Fig. 1. The molecular structure and atom-labeling scheme of (I).
	Fig. 2. The corresponding N—H···O, C—H···O and C—H···F hydrogen bonds stabling the packing structure of (I). Hydrogen bonds are shown as dashed lines.
	Fig. 3. The π-π stacking interactions and N—H···π interactions in (I). Hydrogen bonds are shown as dashed lines.
	Fig. 4. The three-dimensional supramolecular packing architecture of (I). cyan represent π-π stacking interactions and N—H···π interactions while purple represent N—H···O, C—H···F and C—H···O interactions.

Methyl 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetate top

Crystal data top

C₁₁H₈FNO₃	F(000) = 456
M_r = 221.18	D_x = 1.488 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2958 reflections
a = 7.0584 (14) Å	θ = 3.1–27.9°
b = 20.586 (4) Å	µ = 0.12 mm⁻¹
c = 7.3286 (15) Å	T = 113 K
β = 112.01 (3)°	Block, colorless
V = 987.3 (3) Å³	0.30 × 0.24 × 0.20 mm
Z = 4

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2328 independent reflections
Radiation source: rotating anode	2097 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.024
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 3.1°
ω and ϕ scans	h = −9→8
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2004)	k = −27→26
T_min = 0.964, T_max = 0.976	l = −9→9
9472 measured reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.037	w = 1/[σ²(F_o²) + (0.0503P)² + 0.338P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.097	(Δ/σ)_max = 0.001
S = 1.06	Δρ_max = 0.38 e Å⁻³
2328 reflections	Δρ_min = −0.20 e Å⁻³
150 parameters

Crystal data top

C₁₁H₈FNO₃	V = 987.3 (3) Å³
M_r = 221.18	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.0584 (14) Å	µ = 0.12 mm⁻¹
b = 20.586 (4) Å	T = 113 K
c = 7.3286 (15) Å	0.30 × 0.24 × 0.20 mm
β = 112.01 (3)°

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2328 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2004)	2097 reflections with I > 2σ(I)
T_min = 0.964, T_max = 0.976	R_int = 0.024
9472 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.097	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	Δρ_max = 0.38 e Å⁻³
2328 reflections	Δρ_min = −0.20 e Å⁻³
150 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
F1	0.12543 (14)	0.29293 (3)	0.65340 (12)	0.0361 (2)
O1	0.26544 (13)	0.51327 (4)	0.99608 (11)	0.02011 (19)
O2	0.38836 (16)	0.66111 (4)	0.83866 (13)	0.0297 (2)
N1	0.26610 (14)	0.52509 (5)	0.37504 (13)	0.0173 (2)
O3	0.28315 (14)	0.63607 (4)	1.08373 (12)	0.0244 (2)
C1	0.23060 (16)	0.46201 (5)	0.42115 (15)	0.0162 (2)
C2	0.19687 (18)	0.40616 (6)	0.30676 (16)	0.0215 (2)
H2	0.1971	0.4072	0.1772	0.026*
C3	0.16302 (19)	0.34900 (6)	0.38896 (18)	0.0247 (3)
H3	0.1396	0.3095	0.3167	0.030*
C4	0.16368 (19)	0.35010 (5)	0.57927 (18)	0.0232 (3)
C5	0.20002 (17)	0.40431 (5)	0.69689 (16)	0.0187 (2)
H5	0.2012	0.4025	0.8269	0.022*
C6	0.23508 (16)	0.46224 (5)	0.61507 (15)	0.0149 (2)
C7	0.27633 (15)	0.52844 (5)	0.68412 (15)	0.0146 (2)
C8	0.29297 (16)	0.56415 (5)	0.52914 (15)	0.0161 (2)
H8	0.3194	0.6095	0.5323	0.019*
C9	0.28704 (16)	0.55005 (5)	0.87314 (15)	0.0151 (2)
C10	0.32621 (17)	0.62255 (5)	0.92560 (15)	0.0183 (2)
C11	0.3146 (2)	0.70317 (6)	1.14936 (19)	0.0327 (3)
H11A	0.4534	0.7166	1.1666	0.049*
H11B	0.2962	0.7072	1.2749	0.049*
H11C	0.2154	0.7310	1.0508	0.049*
H1	0.271 (2)	0.5363 (8)	0.253 (2)	0.036 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0544 (5)	0.0165 (3)	0.0358 (4)	−0.0065 (3)	0.0150 (4)	0.0025 (3)
O1	0.0294 (4)	0.0200 (4)	0.0134 (4)	−0.0006 (3)	0.0109 (3)	0.0013 (3)
O2	0.0479 (6)	0.0199 (4)	0.0264 (5)	−0.0071 (4)	0.0198 (4)	−0.0019 (3)
N1	0.0195 (5)	0.0220 (5)	0.0121 (4)	0.0002 (3)	0.0079 (4)	0.0007 (3)
O3	0.0397 (5)	0.0183 (4)	0.0178 (4)	0.0013 (3)	0.0141 (4)	−0.0039 (3)
C1	0.0150 (5)	0.0207 (5)	0.0134 (5)	0.0013 (4)	0.0058 (4)	−0.0006 (4)
C2	0.0218 (6)	0.0264 (6)	0.0171 (5)	0.0010 (4)	0.0082 (4)	−0.0057 (4)
C3	0.0263 (6)	0.0214 (5)	0.0247 (6)	0.0004 (4)	0.0077 (5)	−0.0078 (4)
C4	0.0266 (6)	0.0162 (5)	0.0254 (6)	−0.0003 (4)	0.0080 (5)	0.0022 (4)
C5	0.0209 (5)	0.0189 (5)	0.0155 (5)	0.0007 (4)	0.0061 (4)	0.0017 (4)
C6	0.0136 (5)	0.0184 (5)	0.0126 (5)	0.0012 (4)	0.0047 (4)	−0.0003 (4)
C7	0.0149 (5)	0.0174 (5)	0.0120 (5)	0.0011 (4)	0.0056 (4)	0.0009 (4)
C8	0.0167 (5)	0.0191 (5)	0.0130 (5)	0.0002 (4)	0.0061 (4)	0.0010 (4)
C9	0.0161 (5)	0.0170 (5)	0.0125 (5)	0.0010 (4)	0.0056 (4)	0.0000 (4)
C10	0.0219 (5)	0.0190 (5)	0.0130 (5)	0.0017 (4)	0.0054 (4)	−0.0007 (4)
C11	0.0547 (9)	0.0191 (6)	0.0251 (6)	0.0038 (5)	0.0158 (6)	−0.0059 (5)

Geometric parameters (Å, º) top

F1—C4	1.3650 (13)	C3—H3	0.9500
O1—C9	1.2295 (13)	C4—C5	1.3742 (16)
O2—C10	1.1992 (14)	C5—C6	1.3978 (14)
N1—C8	1.3406 (13)	C5—H5	0.9500
N1—C1	1.3881 (14)	C6—C7	1.4450 (14)
N1—H1	0.932 (17)	C7—C8	1.3943 (14)
O3—C10	1.3330 (13)	C7—C9	1.4297 (14)
O3—C11	1.4520 (14)	C8—H8	0.9500
C1—C2	1.3898 (15)	C9—C10	1.5400 (15)
C1—C6	1.4097 (14)	C11—H11A	0.9800
C2—C3	1.3829 (17)	C11—H11B	0.9800
C2—H2	0.9500	C11—H11C	0.9800
C3—C4	1.3932 (17)

C8—N1—C1	109.72 (9)	C5—C6—C7	134.36 (9)
C8—N1—H1	127.7 (10)	C1—C6—C7	106.36 (9)
C1—N1—H1	122.6 (10)	C8—C7—C9	129.44 (10)
C10—O3—C11	115.49 (9)	C8—C7—C6	106.22 (9)
N1—C1—C2	129.26 (10)	C9—C7—C6	124.29 (9)
N1—C1—C6	107.72 (9)	N1—C8—C7	109.97 (9)
C2—C1—C6	123.02 (10)	N1—C8—H8	125.0
C3—C2—C1	117.37 (10)	C7—C8—H8	125.0
C3—C2—H2	121.3	O1—C9—C7	122.84 (10)
C1—C2—H2	121.3	O1—C9—C10	118.29 (9)
C2—C3—C4	119.07 (10)	C7—C9—C10	118.87 (9)
C2—C3—H3	120.5	O2—C10—O3	124.87 (10)
C4—C3—H3	120.5	O2—C10—C9	125.17 (10)
F1—C4—C5	117.96 (11)	O3—C10—C9	109.96 (9)
F1—C4—C3	117.22 (10)	O3—C11—H11A	109.5
C5—C4—C3	124.82 (11)	O3—C11—H11B	109.5
C4—C5—C6	116.43 (10)	H11A—C11—H11B	109.5
C4—C5—H5	121.8	O3—C11—H11C	109.5
C6—C5—H5	121.8	H11A—C11—H11C	109.5
C5—C6—C1	119.27 (9)	H11B—C11—H11C	109.5

C8—N1—C1—C2	−179.36 (11)	C1—C6—C7—C8	0.36 (11)
C8—N1—C1—C6	0.23 (12)	C5—C6—C7—C9	−1.23 (19)
N1—C1—C2—C3	−179.31 (11)	C1—C6—C7—C9	177.96 (10)
C6—C1—C2—C3	1.15 (17)	C1—N1—C8—C7	0.00 (12)
C1—C2—C3—C4	0.19 (17)	C9—C7—C8—N1	−177.67 (10)
C2—C3—C4—F1	178.67 (11)	C6—C7—C8—N1	−0.23 (12)
C2—C3—C4—C5	−1.38 (19)	C8—C7—C9—O1	178.43 (11)
F1—C4—C5—C6	−178.92 (10)	C6—C7—C9—O1	1.41 (17)
C3—C4—C5—C6	1.13 (18)	C8—C7—C9—C10	−1.25 (17)
C4—C5—C6—C1	0.25 (15)	C6—C7—C9—C10	−178.28 (10)
C4—C5—C6—C7	179.36 (12)	C11—O3—C10—O2	0.50 (17)
N1—C1—C6—C5	178.98 (10)	C11—O3—C10—C9	179.76 (10)
C2—C1—C6—C5	−1.40 (16)	O1—C9—C10—O2	164.82 (12)
N1—C1—C6—C7	−0.36 (11)	C7—C9—C10—O2	−15.49 (17)
C2—C1—C6—C7	179.26 (10)	O1—C9—C10—O3	−14.44 (14)
C5—C6—C7—C8	−178.83 (12)	C7—C9—C10—O3	165.25 (9)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3ⁱ	0.932 (17)	2.420 (16)	3.1598 (13)	136.3 (13)
N1—H1···O1ⁱ	0.932 (17)	1.932 (17)	2.7861 (13)	151.3 (14)
C3—H3···F1ⁱⁱ	0.95	2.41	3.3532 (15)	173
C5—H5···O1	0.95	2.55	3.0484 (14)	113
C8—H8···O2	0.95	2.36	2.9049 (14)	116

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

Experimental details

Crystal data
Chemical formula	C₁₁H₈FNO₃
M_r	221.18
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	113
a, b, c (Å)	7.0584 (14), 20.586 (4), 7.3286 (15)
β (°)	112.01 (3)
V (Å³)	987.3 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.30 × 0.24 × 0.20

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2004)
T_min, T_max	0.964, 0.976
No. of measured, independent and observed [I > 2σ(I)] reflections	9472, 2328, 2097
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.097, 1.06
No. of reflections	2328
No. of parameters	150
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.20

Computer programs: CrystalClear (Rigaku/MSC, 2004), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg, 1999), publCIF (Westrip, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3ⁱ	0.932 (17)	2.420 (16)	3.1598 (13)	136.3 (13)
N1—H1···O1ⁱ	0.932 (17)	1.932 (17)	2.7861 (13)	151.3 (14)

Symmetry code: (i) x, y, z−1.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 30873363), the Great Program of the Science Foundation of Tianjin (09ZCKFNC01200) and the Program of the Science Foundation of Tianjin (08JCYBJC070000).

References

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