Ethyl (Z)-4′-(4-eth­oxy-1-hy­droxy-3,4-dioxobut-1-en-1-yl)-[1,1′-biphen­yl]-3-carboxyl­ate

Yoshinobu Ishikawa; Atsushi Ugai

doi:10.1107/S1600536813018503

. 2013 Jul 10;69(Pt 8):o1231. doi: 10.1107/S1600536813018503

Ethyl (Z)-4′-(4-ethoxy-1-hydroxy-3,4-dioxobut-1-en-1-yl)-[1,1′-biphenyl]-3-carboxylate

Yoshinobu Ishikawa ^a,^*, Atsushi Ugai ^a

PMCID: PMC3793735 PMID: 24109322

Abstract

The 1,3-diketone group of the title compound, C₂₁H₂₀O₆, exists in a keto–enol form stabilized by a strong intramolecular O—H⋯O hydrogen bond. As a result, a planar (mean deviation = 0.0099 Å) six-membered hydrogen-bonded ring is formed. The C—O and C—C bond lengths suggest significant electron delocalization in the ring. The dihedral angle between the six-membered hydrogen-bonded ring and its adjacent benzene ring is 8.78 (5)° and that between the benzene rings is 19.70 (5)°. In the crystal, molecules are packed in a layered structure parallel to the b axis through C—H⋯O and π–π interactions [centroid–centroid distance between stacked benzene rings = 3.868 (2) Å].

Related literature

For background to this study, see: Ishikawa & Fujii (2011 ▶). For related structures, see: Wang et al. (2008 ▶); Pillay et al. (2013 ▶). For the biological activity of related compounds, see: Tomassini et al. (1994 ▶). graphic file with name e-69-o1231-scheme1.jpg

Experimental

Crystal data

C₂₁H₂₀O₆
M _r = 368.39
Monoclinic,
a = 26.572 (16) Å
b = 12.194 (5) Å
c = 11.213 (6) Å
β = 96.03 (5)°
V = 3613 (4) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.50 × 0.45 × 0.30 mm

Data collection

Rigaku AFC-7R diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.707, T _max = 0.971
4944 measured reflections
4109 independent reflections
2874 reflections with F ² > 2σ(F ²)
R _int = 0.029
3 standard reflections every 150 reflections intensity decay: 0.7%

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.104
S = 1.01
4109 reflections
250 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: WinAFC (Rigaku, 1999 ▶); cell refinement: WinAFC; data reduction: WinAFC; 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/S1600536813018503/ld2109sup1.cif

e-69-o1231-sup1.cif^{(40.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813018503/ld2109Isup2.hkl

e-69-o1231-Isup2.hkl^{(201.5KB, hkl)}

Click here for additional data file.^{(7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813018503/ld2109Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H14⋯O4	0.98 (3)	1.61 (3)	2.522 (2)	152 (3)

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Acknowledgments

This work was partly supported by Grants-in-Aid (No. 24590141 to YI) for Scientific Research from the Japan Society for the Promotion of Science. We acknowledge the University of Shizuoka for supporting this study.

supplementary crystallographic information

Comment

Biphenyl diketo acids are known to inhibit influenza virus endonuclease (Tomassini et al. 1994). According to our inhibitor design targeting this metalloenzyme (Ishikawa et al. 2011), we synthesized the title compound by Claisen condensation of ethyl 4'-acetyl-[1,1'-biphenyl]-3-carboxylate with diethyl oxalate in the presence of sodium ethoxide, which biphenyl derivatives are the synthetic intermediates of a final biphenyl diketo acid. The 1,3-diketone group exists in keto-enol form stabilized by an intramolecular O–H···O hydrogen bond [O3···O4, 2.522 (2) Å, Table 1], as shown in Figure 1. The distances of C–O [C16–O3 = 1.3063 (18) Å, C18–O4 = 1.2736 (19) Å] and C–C bonds [C16–C17 = 1.403 (2) Å, C17–C18 = 1.396 (3) Å] in the 1,3-diketone group indicate charge delocalization among the atoms. As a result, a six-membered ring formed is essentially plane (mean deviation = 0.0099 Å). The dihedral angles between the six-membered ring and its adjacent benzene ring and between the two benzene rings are 8.78 (5) and 19.70 (5)°, respectively. In the crystal, the molecules are packed as a layered structure through intermolecular C–H···O and π···π interactions, as shown in Figure 2.

Experimental

4'-Acetyl-[1,1'-biphenyl]-3-carboxylate (3.9 mmol), diethyl oxalate (4.7 mmol) and sodium ethoxide (5.4 mmol) were dissolved in ABS. THF (30 ml) and refluxed for 4 h. The reaction mixture was cooled to room temperature, and acidified with 2 M HCl (20 ml). After the mixture was extracted with ethyl acetate, the organic layer was washed with water and brine, and dried over anhydrous Mg₂SO₄. The title compound was obtained by column chromatography on silica gel (n-hexane: ethyl acetate = 3: 1, yield: 40%). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of an ethyl acetate/n-hexane solution of the compound at room temperature.