6-Chloro-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde

Yoshinobu Ishikawa

doi:10.1107/S1600536814014706

. 2014 Jun 25;70(Pt 7):o825. doi: 10.1107/S1600536814014706

6-Chloro-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde

Yoshinobu Ishikawa ^a,^*

PMCID: PMC4120572 PMID: 25161600

Abstract

In the title compound, C₁₀H₄ClFO₃, a chlorinated and fluorinated 3-formylchromone derivative, all atoms are essentially coplanar (r.m.s. = 0.0336 Å for the non-H atoms), with the largest deviation from the least-squares plane [0.062 (2) Å] being for a benzene-ring C atom. In the crystal, molecules are linked through stacking interactions [centroid–centroid distance between the benzene and pyran rings = 3.958 (3) Å and interplanar distance = 3.259 (3) Å], C—H⋯O hydrogen bonds, and short C⋯O contacts [2.879 (3) Å]. Unsymmetrical halogen–halogen interactions between the Cl and F atoms [Cl⋯F = 3.049 (3) Å, C—Cl⋯F = 148.10 (9)° and C—F⋯Cl = 162.06 (13)°] are also formed, giving a meandering two-dimensional network along the a axis.

Keywords: crystal structure

Related literature

For related structures, see: Ishikawa & Motohashi (2013 ▶); Ishikawa (2014 ▶). For halogen bonding, see: Auffinger et al. (2004 ▶); Metrangolo et al. (2005 ▶); Wilcken et al. (2013 ▶); Sirimulla et al. (2013 ▶). For halogen–halogen interactions, see: Hathwar & Guru Row (2011 ▶); Metrangolo & Resnati (2014 ▶); Mukherjee & Desiraju (2014 ▶). graphic file with name e-70-0o825-scheme1.jpg

Experimental

Crystal data

C₁₀H₄ClFO₃
M _r = 226.59
Orthorhombic,
a = 5.725 (3) Å
b = 32.57 (3) Å
c = 4.706 (4) Å
V = 877.4 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.43 mm⁻¹
T = 100 K
0.40 × 0.25 × 0.08 mm

Data collection

Rigaku AFC-7R diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.894, T _max = 0.966
1692 measured reflections
1346 independent reflections
1249 reflections with F ² > 2σ(F ²)
R _int = 0.009
3 standard reflections every 150 reflections intensity decay: −0.1%

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.074
S = 1.09
1346 reflections
136 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.25 e Å⁻³
Absolute structure: Flack (1983 ▶), 105 Friedel Pairs
Absolute structure parameter: 0.31 (9)

Data collection: WinAFC Diffractometer Control Software (Rigaku, 1999 ▶; cell refinement: WinAFC Diffractometer Control Software; data reduction: WinAFC Diffractometer Control Software; program(s) used to solve structure: SIR2008 (Burla et al., 2007 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: CrystalStructure (Rigaku, 2010 ▶); software used to prepare material for publication: CrystalStructure.

Supplementary Material

Crystal structure: contains datablock(s) General, I. DOI: 10.1107/S1600536814014706/zl2593sup1.cif

e-70-0o825-sup1.cif^{(24KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814014706/zl2593Isup2.hkl

e-70-0o825-Isup2.hkl^{(66.5KB, hkl)}

Click here for additional data file.^{(3.4KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814014706/zl2593Isup3.cml

CCDC reference: 1009489

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H3⋯O2ⁱ	0.95	2.27	3.173 (3)	158
C1—H1⋯O3ⁱⁱ	0.95	2.40	3.242 (3)	147

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

I acknowledge the University of Shizuoka for instrumental support.

supplementary crystallographic information

S1. Comment

Halogen bonding and halogen···halogen interactions have recently attracted much attention in medicinal chemistry, chemical biology, supramolecular chemistry and crystal engineering (Auffinger et al., 2004, Metrangolo et al., 2005, Wilcken et al., 2013, Sirimulla et al., 2013, Mukherjee et al., 2014, Metrangolo et al., 2014). We have recently reported the crystal structures of chlorinated 3-formylchromone derivatives 6,8-dichloro-4-oxochromene-3-carbaldehyde (Ishikawa & Motohashi, 2013) and 6-chloro-4-oxo-4H-chromene-3-carbaldehyde (Ishikawa, 2014). Halogen bonding between the formyl oxygen atom and the chlorine atom at the 8-position and type I halogen···halogen interaction between the chlorine atoms at 6-position are observed in 6,8-dichloro-4-oxochromene-3-carbaldehyde (Fig.3 (top)). On the other hand, a van der Waals contact between the formyl oxygen atom and the chlorine atom at 6-position is found in 6-chloro-4-oxo-4H-chromene-3-carbaldehyde (Fig.3 (middle)). As part of our interest in these types of chemical bonding, we herein report the crystal structure of a monochlorinated and monofluorinated 3-formylchromone derivative, 6-chloro-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde. The objective of this study is to reveal the inductive effect of the vicinal electron-withdrawing substituent on the chlorine atom at 6-position and the interaction mode(s).

The mean deviation of the least-square planes for the non-hydrogen atoms is 0.0336 Å, and the largest deviations is 0.062 (2) Å for C4. These mean that these atoms are essentially coplanar (Fig.1).

In the crystal, the molecules are linked through stacking interaction between the translation-symmetry equivalentⁱ molecules [centroid–centroid distance between the benzene and pyran rings of the 4H-chromene units = 3.958 (3) Å, interplanar distance 3.259 (3) Å, i: x, y, z + 1], and through C–H···O hydrogen bonds (see hydrogen bonding table).

A contact between the formyl oxygen atom and the chlorine atom at 6-position is not found in the title compound. Instead, unsymmetrical halogen···halogen interactions are formed between the chlorine and fluorine atoms [Cl1···F1 = 3.049 (3) Å, C5–Cl1···F1 = 148.10 (9)°, C6–F1···Cl1 = 162.06 (13)°] to give a meandering two-dimensional-network along the a axis, as shown in Fig.2 and Fig.3 (bottom). It is suggested that the electron-withdrawing substituent at 7-position should make the σ-hole of the chlorine atom at 6-position larger, and the electropositive region of the chlorine atom should contact the electronegative region of the fluorine atom (Hathwar et al., 2011). Symmetrical halogen···halogen interactions (F···F and Cl···Cl) are not observed in the title compound, which might support that the unsymmetrical Cl···F interaction is more favorable than the symmetrical ones.

Furthermore, short contacts between the formyl C10 and O3ⁱⁱ atoms [2.879 (3) Å, ii: –x + 1/2, –y + 1, z + 1/2] are observed. This interesting feature might be caused by strong dipole-dipole interaction between the formyl groups polarized by introduction of the chlorine and fluorine atoms into the chromone ring. These findings should be helpful to understand interaction of halogenated ligands with proteins, and are thus valuable for rational drug design.

S2. Experimental

5-Chloro-4-fluoro-2-hydroxyacetophenone was prepared from 4-chloro-3-fluorophenol by Fries rearrangement reaction. To a solution of 5-chloro-4-fluoro-2-hydroxyacetophenone (2.4 mmol) in N,N-dimethylformamide (10 ml) was added dropwise POCl₃ (6.0 mmol) at 0 °C. After the mixture was stirred for 14 h at room temperature, water (30 ml) was added. The precipitates were collected, washed with water, and dried in vacuo (yield: 58%). ¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, 1H, J = 8.3 Hz), 8.37 (d, 1H, J = 8.3 Hz), 8.52 (s, 1H), 10.36 (s, 1H). DART-MS calcd for [C₁₀H₄Cl₁F₁O₃ + H⁺]: 226.991, found 227.014. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of an ethyl acetate/chloroform solution of the title compound at room temperature.