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Acta Cryst. (2011). E67, o905    [ doi:10.1107/S1600536811009378 ]

1-Methyl-3-(2-methylphenyl)-3,3a,4,9b-tetrahydro-1H-chromeno[4,3-c][1,2]oxazole-3a-carbonitrile

K. Swaminathan, K. Sethusankar, G. Murugan and M. Bakthadoss

Abstract top

In the title compound, C19H18N2O2, the five-membered isoxazole ring adopts an envelope conformation and the deviation of the N atom from the mean plane of the isoxazole ring is -0.3256 (11) Å. The pyran ring adopts a half-chair conformation. The isoxazole ring forms dihedral angles of 44.07 (7) and 84.23 (7)° with the pyran and methylbenzene rings, respectively. The molecular structure is stabilized by weak C-H...[pi] interactions.

Comment top

The title compound is an angularly substituted fused tricyclic chromenoisoxazolidine framework, synthesized using Baylis-Hillman derivatives through in situ formation of nitrones followed by an intramolecular (3 + 2) dipolar cycloaddition reaction sequence (Bakthadoss & Murugan, 2010). It is well known that benzopyran and isoxazolidine derivatives possess interesting biological and pharmacological activities (Lin et al., 1996; Hu et al., 2004). Leflunomide is an isoxazole drug used for the treatment of rheumatoid arthritis (Rozman et al., 2002).

The title compound (Fig. 1) comprises a chromenoisoxazole ring system attached to a methylbenzene ring and a carbonitrile group. The isoxazole ring (N1/O2/C7/C8/C10) adopts an N1 envelope conformation with N1 -0.3256 (11) Å out of the plane formed by the rest of the ring atoms. The isoxazole ring is inclined at 84.23 (7)° with respect to the mean-plane formed by methylbenzene ring (C11—C16). The pyran ring (O1/C1/C6-C9) adopts a half-chair conformation with puckering amplitudes (Cremer & Pople, 1975): Q = 0.4852 (13) Å, θ = 127.2 (2)° and φ = 107.9 (2)°. The title compound exhibits structural similarities with a reported structure (Swaminathan et al., 2011). The molecular structure of the title compound is stabilized by rather weak C18—H18B···π interactions involving the centroid (Cg1) of phenyl ring C11–C16 (Table 1).

Related literature top

For synthetic aspects, see: Bakthadoss et al. (2010). For biological and pharmacological activities of isoxazole derivatives, see: Hu et al. (2004); Lin et al. (1996); Rozman et al. (2002). For a related structure, see: Swaminathan et al. (2011). For puckering amplitudes, see: Cremer & Pople (1975).

Experimental top

A mixture of (E)-2-((2-formylphenoxy) methyl) -3-o-tolylacrylonitrile (1.0 mmol), N-methylhydroxylamine hydrochloride (1.1 mmol), pyridine (0.24 ml, 3 mmol) and ethanol (5 ml) were placed in a round bottom flask and refluxed for 6 h. After completion of the reaction as indicated by TLC, the reaction mixture was concentrated under reduced pressure. The crude product was diluted with water (10 ml) and dil HCl (5 ml) and extracted with ethylacetate (20 ml). The organic layer was washed with brine solution (10 ml) and concetrated. The crude product was purified by column chromatography to provide the pure title compound, as a colourless solid. Crystals of the title compound were grown from its solution in methanol by slow evaporation at room temperature.

Refinement top

Hydrogen atoms were placed in calculated positions with C—H = 0.93, 0.96, 0.97 and 0.98 Å for aryl, methyl, methylene and methyne type H-atoms, respectively, and refined in riding model with fixed isotropic displacement parameters: Uiso(H) = 1.5 Ueq(methyl-C) and Uiso(H) = 1.2 Ueq(the rest of the C atoms).

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at 30% probability level. H atoms are drawn as small spheres of arbitary radius.
1-Methyl-3-(2-methylphenyl)-3,3a,4,9b-tetrahydro-1H- chromeno[4,3-c][1,2]oxazole-3a-carbonitrile top
Crystal data top
C19H18N2O2F(000) = 648
Mr = 306.35Dx = 1.278 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -p 2ynCell parameters from 5936 reflections
a = 11.0120 (4) Åθ = 1.0–25°
b = 13.0368 (4) ŵ = 0.08 mm−1
c = 11.1977 (3) ÅT = 293 K
β = 97.836 (2)°Block, colourless
V = 1592.54 (9) Å30.30 × 0.25 × 0.20 mm
Z = 4
Data collection top
Bruker Kappa APEXII CCD
diffractometer		3084 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.035
graphiteθmax = 33.1°, θmin = 2.4°
ω scansh = −15→16
23069 measured reflectionsk = −18→19
5936 independent reflectionsl = −14→17
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.051Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.148H-atom parameters constrained
S = 1.01 w = 1/[σ2(Fo2) + (0.0684P)2 + 0.0556P]
where P = (Fo2 + 2Fc2)/3
5936 reflections(Δ/σ)max < 0.001
210 parametersΔρmax = 0.18 e Å−3
0 restraintsΔρmin = −0.21 e Å−3
Crystal data top
C19H18N2O2V = 1592.54 (9) Å3
Mr = 306.35Z = 4
Monoclinic, P21/nMo Kα radiation
a = 11.0120 (4) ŵ = 0.08 mm−1
b = 13.0368 (4) ÅT = 293 K
c = 11.1977 (3) Å0.30 × 0.25 × 0.20 mm
β = 97.836 (2)°
Data collection top
Bruker Kappa APEXII CCD
diffractometer		3084 reflections with I > 2σ(I)
23069 measured reflectionsRint = 0.035
5936 independent reflectionsθmax = 33.1°
Refinement top
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.148Δρmax = 0.18 e Å−3
S = 1.01Δρmin = −0.21 e Å−3
5936 reflectionsAbsolute structure: ?
210 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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 (Å2) top
xyzUiso*/Ueq
C10.38107 (11)0.12807 (10)0.10789 (11)0.0446 (3)
C20.43271 (13)0.21739 (11)0.15852 (13)0.0582 (4)
H20.47060.21780.23800.070*
C30.42782 (15)0.30530 (12)0.09094 (15)0.0654 (4)
H30.46350.36520.12450.078*
C40.37052 (14)0.30563 (12)−0.02619 (15)0.0640 (4)
H40.36850.3653−0.07200.077*
C50.31626 (13)0.21749 (10)−0.07520 (13)0.0536 (3)
H50.27540.2187−0.15350.064*
C60.32143 (11)0.12627 (9)−0.00950 (10)0.0425 (3)
C70.25834 (11)0.03122 (9)−0.06218 (10)0.0407 (3)
H70.17450.0473−0.09870.049*
C80.25759 (10)−0.05625 (9)0.02964 (10)0.0396 (3)
C90.37624 (12)−0.05094 (10)0.11822 (11)0.0458 (3)
H9A0.3776−0.10680.17560.055*
H9B0.4458−0.05930.07440.055*
C100.25780 (11)−0.15460 (10)−0.05147 (10)0.0448 (3)
H100.3344−0.1923−0.02880.054*
C110.15148 (11)−0.22621 (9)−0.04883 (10)0.0430 (3)
C120.03836 (12)−0.19982 (11)−0.11130 (12)0.0528 (3)
H120.0313−0.1411−0.15890.063*
C13−0.06361 (13)−0.25916 (12)−0.10388 (13)0.0577 (4)
H13−0.1390−0.2407−0.14620.069*
C14−0.05336 (13)−0.34544 (11)−0.03398 (13)0.0571 (4)
H14−0.1221−0.3854−0.02780.069*
C150.05804 (14)−0.37299 (10)0.02683 (12)0.0544 (3)
H150.0638−0.43220.07350.065*
C160.16284 (12)−0.31509 (10)0.02085 (10)0.0458 (3)
C170.28229 (15)−0.35091 (13)0.08907 (14)0.0714 (4)
H17A0.3372−0.36980.03310.107*
H17B0.2679−0.40920.13760.107*
H17C0.3181−0.29660.14000.107*
C180.31258 (15)0.02789 (12)−0.26883 (11)0.0624 (4)
H18A0.3441−0.0171−0.32510.094*
H18B0.35740.0912−0.26410.094*
H18C0.22750.0413−0.29530.094*
C190.15272 (11)−0.05003 (9)0.09694 (11)0.0439 (3)
N10.32585 (9)−0.02011 (8)−0.15097 (8)0.0464 (3)
N20.07493 (11)−0.04521 (10)0.15340 (10)0.0598 (3)
O10.38708 (8)0.04332 (7)0.18095 (7)0.0501 (2)
O20.25538 (9)−0.11520 (7)−0.17000 (7)0.0540 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0477 (6)0.0468 (7)0.0411 (6)−0.0039 (5)0.0120 (5)−0.0003 (5)
C20.0646 (8)0.0602 (9)0.0508 (7)−0.0107 (7)0.0116 (6)−0.0100 (7)
C30.0768 (10)0.0492 (9)0.0737 (10)−0.0142 (7)0.0224 (8)−0.0106 (8)
C40.0764 (10)0.0434 (8)0.0756 (10)−0.0011 (7)0.0229 (8)0.0065 (7)
C50.0592 (8)0.0497 (8)0.0530 (7)0.0026 (6)0.0116 (6)0.0084 (6)
C60.0446 (6)0.0427 (7)0.0416 (6)0.0008 (5)0.0116 (5)0.0013 (5)
C70.0426 (6)0.0460 (7)0.0341 (5)−0.0010 (5)0.0071 (4)0.0045 (5)
C80.0436 (6)0.0430 (7)0.0332 (5)−0.0024 (5)0.0089 (4)0.0016 (5)
C90.0518 (7)0.0487 (7)0.0370 (6)−0.0009 (6)0.0060 (5)0.0052 (5)
C100.0519 (7)0.0451 (7)0.0392 (6)0.0005 (5)0.0128 (5)−0.0001 (5)
C110.0529 (7)0.0397 (7)0.0379 (5)−0.0008 (5)0.0121 (5)−0.0041 (5)
C120.0604 (8)0.0440 (7)0.0544 (7)0.0017 (6)0.0087 (6)0.0031 (6)
C130.0516 (7)0.0597 (9)0.0617 (8)−0.0006 (6)0.0072 (6)−0.0070 (7)
C140.0609 (8)0.0535 (8)0.0600 (8)−0.0130 (7)0.0192 (7)−0.0093 (7)
C150.0768 (9)0.0427 (7)0.0461 (7)−0.0094 (6)0.0168 (6)−0.0025 (6)
C160.0623 (8)0.0398 (7)0.0360 (6)−0.0005 (6)0.0098 (5)−0.0036 (5)
C170.0772 (10)0.0690 (11)0.0641 (9)−0.0002 (8)−0.0049 (8)0.0154 (8)
C180.0810 (10)0.0714 (10)0.0372 (6)−0.0130 (8)0.0161 (6)0.0050 (6)
C190.0513 (7)0.0423 (7)0.0394 (6)−0.0030 (5)0.0102 (5)0.0016 (5)
N10.0557 (6)0.0498 (6)0.0361 (5)−0.0091 (5)0.0146 (4)0.0002 (4)
N20.0639 (7)0.0652 (8)0.0551 (7)0.0023 (6)0.0249 (6)0.0060 (6)
O10.0622 (5)0.0532 (6)0.0340 (4)−0.0076 (4)0.0040 (4)0.0004 (4)
O20.0737 (6)0.0535 (6)0.0374 (4)−0.0161 (4)0.0166 (4)−0.0045 (4)
Geometric parameters (Å, °) top
C1—O11.3710 (14)C10—C111.5008 (17)
C1—C21.3830 (18)C10—H100.9800
C1—C61.3872 (17)C11—C121.3864 (18)
C2—C31.370 (2)C11—C161.3928 (17)
C2—H20.9300C12—C131.3754 (19)
C3—C41.376 (2)C12—H120.9300
C3—H30.9300C13—C141.366 (2)
C4—C51.374 (2)C13—H130.9300
C4—H40.9300C14—C151.367 (2)
C5—C61.3954 (17)C14—H140.9300
C5—H50.9300C15—C161.3882 (18)
C6—C71.5015 (17)C15—H150.9300
C7—N11.4800 (15)C16—C171.5027 (19)
C7—C81.5363 (16)C17—H17A0.9600
C7—H70.9800C17—H17B0.9600
C8—C191.4647 (16)C17—H17C0.9600
C8—C91.5305 (16)C18—N11.4498 (16)
C8—C101.5715 (17)C18—H18A0.9600
C9—O11.4124 (15)C18—H18B0.9600
C9—H9A0.9700C18—H18C0.9600
C9—H9B0.9700C19—N21.1336 (16)
C10—O21.4201 (14)N1—O21.4626 (13)
O1—C1—C2116.76 (11)O2—C10—H10109.2
O1—C1—C6122.00 (11)C11—C10—H10109.2
C2—C1—C6121.18 (12)C8—C10—H10109.2
C3—C2—C1119.65 (14)C12—C11—C16119.67 (11)
C3—C2—H2120.2C12—C11—C10119.03 (11)
C1—C2—H2120.2C16—C11—C10121.18 (11)
C2—C3—C4120.50 (14)C13—C12—C11120.98 (13)
C2—C3—H3119.8C13—C12—H12119.5
C4—C3—H3119.8C11—C12—H12119.5
C5—C4—C3119.73 (14)C14—C13—C12119.56 (13)
C5—C4—H4120.1C14—C13—H13120.2
C3—C4—H4120.1C12—C13—H13120.2
C4—C5—C6121.18 (13)C13—C14—C15120.00 (13)
C4—C5—H5119.4C13—C14—H14120.0
C6—C5—H5119.4C15—C14—H14120.0
C1—C6—C5117.72 (12)C14—C15—C16121.90 (13)
C1—C6—C7121.34 (11)C14—C15—H15119.1
C5—C6—C7120.85 (11)C16—C15—H15119.1
N1—C7—C6112.90 (9)C15—C16—C11117.88 (12)
N1—C7—C899.38 (9)C15—C16—C17118.83 (12)
C6—C7—C8113.21 (9)C11—C16—C17123.28 (12)
N1—C7—H7110.3C16—C17—H17A109.5
C6—C7—H7110.3C16—C17—H17B109.5
C8—C7—H7110.3H17A—C17—H17B109.5
C19—C8—C9109.11 (9)C16—C17—H17C109.5
C19—C8—C7112.33 (9)H17A—C17—H17C109.5
C9—C8—C7108.55 (9)H17B—C17—H17C109.5
C19—C8—C10113.95 (9)N1—C18—H18A109.5
C9—C8—C10110.06 (10)N1—C18—H18B109.5
C7—C8—C10102.61 (9)H18A—C18—H18B109.5
O1—C9—C8111.62 (10)N1—C18—H18C109.5
O1—C9—H9A109.3H18A—C18—H18C109.5
C8—C9—H9A109.3H18B—C18—H18C109.5
O1—C9—H9B109.3N2—C19—C8177.11 (13)
C8—C9—H9B109.3C18—N1—O2104.33 (9)
H9A—C9—H9B108.0C18—N1—C7114.76 (11)
O2—C10—C11109.16 (10)O2—N1—C7100.14 (8)
O2—C10—C8104.11 (9)C1—O1—C9114.23 (9)
C11—C10—C8115.69 (9)C10—O2—N1103.20 (8)
O1—C1—C2—C3−178.84 (12)C9—C8—C10—C11123.40 (11)
C6—C1—C2—C3−1.6 (2)C7—C8—C10—C11−121.21 (11)
C1—C2—C3—C40.9 (2)O2—C10—C11—C12−41.16 (15)
C2—C3—C4—C50.9 (2)C8—C10—C11—C1275.80 (14)
C3—C4—C5—C6−2.0 (2)O2—C10—C11—C16142.76 (11)
O1—C1—C6—C5177.60 (11)C8—C10—C11—C16−100.28 (13)
C2—C1—C6—C50.56 (18)C16—C11—C12—C131.17 (19)
O1—C1—C6—C70.98 (18)C10—C11—C12—C13−174.97 (12)
C2—C1—C6—C7−176.06 (11)C11—C12—C13—C140.0 (2)
C4—C5—C6—C11.29 (19)C12—C13—C14—C15−0.8 (2)
C4—C5—C6—C7177.93 (12)C13—C14—C15—C160.5 (2)
C1—C6—C7—N1−106.66 (12)C14—C15—C16—C110.60 (19)
C5—C6—C7—N176.83 (14)C14—C15—C16—C17−179.31 (13)
C1—C6—C7—C85.29 (16)C12—C11—C16—C15−1.42 (17)
C5—C6—C7—C8−171.23 (10)C10—C11—C16—C15174.63 (11)
N1—C7—C8—C19−152.86 (9)C12—C11—C16—C17178.48 (13)
C6—C7—C8—C1987.13 (12)C10—C11—C16—C17−5.46 (18)
N1—C7—C8—C986.40 (10)C6—C7—N1—C18−77.73 (13)
C6—C7—C8—C9−33.60 (13)C8—C7—N1—C18162.04 (10)
N1—C7—C8—C10−30.08 (10)C6—C7—N1—O2171.21 (9)
C6—C7—C8—C10−150.08 (10)C8—C7—N1—O250.98 (10)
C19—C8—C9—O1−62.50 (12)C2—C1—O1—C9−157.77 (11)
C7—C8—C9—O160.20 (12)C6—C1—O1—C925.06 (16)
C10—C8—C9—O1171.77 (9)C8—C9—O1—C1−56.41 (13)
C19—C8—C10—O2120.23 (10)C11—C10—O2—N1157.42 (9)
C9—C8—C10—O2−116.84 (10)C8—C10—O2—N133.34 (11)
C7—C8—C10—O2−1.45 (11)C18—N1—O2—C10−173.44 (10)
C19—C8—C10—C110.47 (15)C7—N1—O2—C10−54.44 (11)
Hydrogen-bond geometry (Å, °) top
Cg1 is the centroid of the phenyl ring C11–C16.
D—H···AD—HH···AD···AD—H···A
C18—H18B···Cg1i0.962.993.6831 (16)130
Symmetry codes: (i) −x+1/2, y+1/2, −z−1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
Cg1 is the centroid of the phenyl ring C11–C16.
D—H···AD—HH···AD···AD—H···A
C18—H18B···Cg1i0.962.993.6831 (16)130
Symmetry codes: (i) −x+1/2, y+1/2, −z−1/2.
Acknowledgements top

K. Swaminathan and K. Sethusankar thank Dr Babu Varghese, SAIF, IIT, Chennai, India, for the X-ray intensity data collection.

references
References top

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