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

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].

Key indicators

• Single-crystal X-ray study
• T = 113 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.037
• wR factor = 0.097
• Data-to-parameter ratio = 15.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT369_ALERT_2_C Long   C(sp2)-C(sp2) Bond  C9     -   C10    ...       1.54 Ang.
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          1
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         16
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          6
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         14

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

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

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).

S2. Experimental

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.

S3. Refinement

H atoms on N atoms were located in a difference Fourier map and refined isotropically, with restrains of N—H = 0.90±0.01 Å. Other H atoms were positioned geometrically with C—H = 0.93 and 0.96 Å, for indole H atoms, respectively, and refined using a riding model, with U_iso(H) =1.2Ueq(C)(1.5 for methyl groups).

Computing details

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

	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

Crystal data

C11H8FNO3	F(000) = 456
Mr = 221.18	Dx = 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) Å^3	0.30 × 0.24 × 0.20 mm
Z = 4

Data collection

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

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.037	w = 1/[σ^2(Fo^2) + (0.0503P)^2 + 0.338P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.097	(Δ/σ)max = 0.001
S = 1.06	Δρmax = 0.38 e Å^−3
2328 reflections	Δρmin = −0.20 e Å^−3
150 parameters

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3^i	0.932 (17)	2.420 (16)	3.1598 (13)	136.3 (13)
N1—H1···O1^i	0.932 (17)	1.932 (17)	2.7861 (13)	151.3 (14)
C3—H3···F1^ii	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.