rac-3-(4-Chloro­phen­yl)-3a,4-di­hydro-3H-chromeno[4,3-c]isoxazole-3a-carbo­nitrile

S Paramasivam; J Srinivasan; PR Seshadri; M Bakthadoss

doi:10.1107/S1600536813009653

. 2013 Apr 13;69(Pt 5):o716. doi: 10.1107/S1600536813009653

rac-3-(4-Chlorophenyl)-3a,4-dihydro-3H-chromeno[4,3-c]isoxazole-3a-carbonitrile

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

PMCID: PMC3648249 PMID: 23723869

Abstract

The title compound, C₁₇H₁₁ClN₂O₂, which contains two stereogenic C atoms, crystallizes in a centrosymmetric space group as a racemate. The pyran ring and the 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 4.17 (5)°. The molecular conformation features a weak C—H⋯O contact. In the crystal, C—H⋯O hydrogen bonds link the molecules, forming chains along the a-axis direction.

Related literature

For the biological activity of isoxazole derivatives, see: Mullen et al. (1988 ▶); Eddington et al. (2002 ▶); Kashiwada et al. (2001 ▶); Caine (1993 ▶). For a related structure, see: Paramasivam et al. (2012 ▶). For conformational analysis and pukering parameters, see: Cremer & Pople (1975 ▶). graphic file with name e-69-0o716-scheme1.jpg

Experimental

Crystal data

C₁₇H₁₁ClN₂O₂
M _r = 310.73
Monoclinic,
a = 6.7891 (2) Å
b = 13.9921 (3) Å
c = 15.1788 (3) Å
β = 101.175 (1)°
V = 1414.55 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 298 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.921, T _max = 0.946
13620 measured reflections
3541 independent reflections
2865 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.132
S = 1.00
3541 reflections
199 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.37 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 for Windows (Farrugia, 2012 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97, PLATON and publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(24.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813009653/kp2448sup1.cif

e-69-0o716-sup1.cif^{(24.6KB, cif)}

Click here for additional data file.^{(170.1KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813009653/kp2448Isup2.hkl

e-69-0o716-Isup2.hkl^{(170.1KB, hkl)}

Click here for additional data file.^{(5.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813009653/kp2448Isup3.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
C13—H13⋯O1	0.93	2.42	2.7733 (19)	102
C5—H5⋯O2ⁱ	0.93	2.47	3.3422 (19)	156

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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

As a continuation of our research related to isoxazole containing chromenoisoxazole moiety, we analysed the crystal structure of rac-6-Ethoxy-3,3a,4,9 b-tetrahydro-1,3- diphenyl-1H-chromeno[4,3-c]isoxazole- 3a-carbonitrile (Paramasivam et al., 2012). The present compound exhibits the pronounced similarity to the previous ones, either in bond lengths and angles as well as in molecular conformations.

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

The pyran ring (O2/C1/C6—C9) adopts a sofa conformation with the puckering parameters (Cremer & Pople, 1975) being q₂=0.359 (1) Å, q₃=-0.292 (1) Å, Q_T=0.463 (1) Å and the five-membered isoxazole ring (N1/O1/C7/C8/C11) adopts an envelope conformation with puckering parameters (Cremer & Pople, 1975) being q₂=0.284 (1) Å and Φ₂=142.4 (3)°.

The dihedral angle between the pyran and the benzene rings (C1—C6) is 4.17 (5)°. The dihedral angle between the chromeno ring (fusion of benzene and pyran rings) and isoxazole ring is 13.42 (5)°. In the chromenoisoxazole moiety, the dihedral angle between the benzene and isoxazole ring is 10.83 (5)° and the dihedral angle between the pyran and isoxazole ring is 14.81 (5)°.

The geometric parameters of the title compound (Fig. 1) agree well with the reported ones of similar structures (Paramasivam et al., 2012).

The molecular structure is stabilized by C—H···O intramolecular interaction and the crystal packing is stabilized by C—H···O hydrogen bonds (Table 1).

Experimental

A solution of (E)-3-(4-chlorophenyl)-2-((2-((E)-(hydroxyimino)methyl)phenoxy)methyl) acrylonitrile (2 mmol) in CCl₄ at (273–283 K) was added pinch wise NCS (4 mmol) over 3 h. After Et₃N (4 mmol) was added the reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, reaction mixture was evaporated under reduced pressure and the resulting crude mass was diluted with water (15 mL) and extracted with ethyl acetate (3 × 15 mL). The combining organic layer was washed with brine (2 × 10 mL) and dried over anhydrous Na₂SO₄. The organic layer was evaporated and purified by column chromatography (silica gel 60–120 mesh 7% EtOAc in hexanes) to provide the desired pure product 3-(4-chlorophenyl)-3a,4-dihydro-3H-chromeno[4,3-c]isoxazole-3a-carbonitrile a as colourless solid.