rac-Methyl 3-(2-meth­oxy­phen­yl)-1-phenyl-3,3a,4,9b-tetra­hydro-1H-chromeno[4,3-c]isoxazole-3a-carboxyl­ate

S Paramasivam; J Srinivasan; P R Seshadri; M Bakthadoss

doi:10.1107/S1600536812021356

. 2012 Jun 2;68(Pt 7):o1987. doi: 10.1107/S1600536812021356

rac-Methyl 3-(2-methoxyphenyl)-1-phenyl-3,3a,4,9b-tetrahydro-1H-chromeno[4,3-c]isoxazole-3a-carboxylate

S Paramasivam ^a, J Srinivasan ^b, P R Seshadri ^a,^*, M Bakthadoss ^b

PMCID: PMC3393263 PMID: 22807820

Abstract

The title compound, C₂₅H₂₃NO₅, comprising two stereogenic carbon atoms of the same configuration, crystallizes in a centrosymmetric space group as a racemate. The six-membered pyran ring and the five-membered isoxazole ring adopt sofa and twisted conformations, respectively. The dihedral angle between the benzene ring and the mean plane through the near coplanar atoms of the pyran ring is 10.73 (7)°. The crystal structure features C—H⋯O hydrogen bonds.

Related literature

For the biological activity of the title compound, see: Eddington et al. (2002 ▶); Mullen et al. (1988 ▶); Kashiwada et al. (2001 ▶); Caine (1993 ▶). For N-atom hybridization, see: Beddoes et al. (1986 ▶). For related structures, see: Kanchanadevi et al. (2011 ▶); Swaminathan et al. (2012 ▶). For conformational analysis and puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₅H₂₃NO₅
M _r = 417.44
Monoclinic,
a = 18.3791 (7) Å
b = 15.2466 (6) Å
c = 7.7235 (3) Å
β = 90.514 (2)°
V = 2164.18 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.20 × 0.15 × 0.10 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
20989 measured reflections
5478 independent reflections
3614 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.159
S = 0.96
5478 reflections
280 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008 ▶), PLATON and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812021356/kp2411sup1.cif

e-68-o1987-sup1.cif^{(30.9KB, cif)}

Structure factors: contains datablock(s) guru2. DOI: 10.1107/S1600536812021356/kp2411Isup2.hkl

e-68-o1987-Isup2.hkl^{(268.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812021356/kp2411Isup3.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
C7—H7⋯O4	0.98	2.33	2.803 (2)	109
C15—H15⋯O3ⁱ	0.93	2.42	3.285 (3)	155

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge the Technology Business Incubator (TBI), CAS in Crystallography, University of Madras, Chennai 600 025, India, for the data collection.

supplementary crystallographic information

Comment

Isoxazole derivative exhibit anti-consulvant (Eddington et al., 2002) and anti-fungal (Mullen et al., 1988) activities, whereas benzopyran and chromenopyrrole derivatives are used in the treatment of impulsive-disorder disease (Caine, 1993) and exhibit anti-HIV activities (Kashiwada et al., 2001). On this grounds, the title compound was chosen for X-ray structure analysis (Fig.1).

The pyran ring (O1/C1/C6—C9) adopts a sofa conformation with the puckering parameters (Cremer & Pople, 1975) being q₂=0.478 (2) Å, q₃=0.230 (2) Å, Q_T=0.531 (2) Å and the five membered ring isoxazole (O2/N1/C7/C8/C12) adopts a twisted conformation with puckering parameters (Cremer & Pople, 1975) being q₂=0.429 (1) Å and Φ₂=165.9 (2)°. The dihedral angle between the pyran and the benzene ring (C1—C6) is 10.73 (7)°. The dihedral angle between the chromeno ring (fusion of benzene and pyran rings) and isoxazole ring is 57.52 (5)°.

In the chromenoisoxazole moiety, the dihedral angle between the benzene and isoxazole ring is 56.88 (6)°. The dihedral angle between the pyran and isoxazole ring is 56.27 (6)°. The sum of the bond angles around N1 [334.55 (39)°] indicates sp3 hybridization (Beddoes et al.,1986). The unit cell contains no residual solvent accessible voids, if the voids in the dry crystals ever contained solvent, though generally solvent loss from organic crystals is associated with either a total loss of crystallinity or at least a degradation of the crystal quality. In this case the crystals remained glass-clear.

The geometric parameters of the title compound (Fig. 1) agree well with the reported similar structures (Kanchanadevi et al., 2011; Swaminathan et al., 2012).

The molecular structure is stabilized by C— H··· O intramolecular interactions and the crystal packing is via C— H··· O hydrogen bonds(Table 1, Fig. 2).

Experimental

A mixture of (E)-methyl 2-((2-formylphenoxy)methyl)-3-(2-methoxyphenyl)acrylate (2 mmol, 0.65 g) and N-phenylhydroxylamine (3 mmol, 0.33 g) in ethanol (10 mL) was refluxed for 6 h. After the completion of the reaction as indicated by TLC, the reaction mixture was concentrated and the resulting crude mass was diluted with water (15 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layer was washed with brine (3 × 15 mL) and dried over anhydrous Na₂SO₄, solvent was removed under reduced pressure. The crude mass was purified by column chromatography on silica gel (Acme 100–200 mesh), using ethyl acetate-hexane (0.5: 9.5) to afford the pure compound as a colourless solid in 91% yield.