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Acta Crystallogr Sect E Struct Rep Online. 2009 September 1; 65(Pt 9): o2207.
Published online 2009 August 22. doi:  10.1107/S1600536809032462
PMCID: PMC2970144

Dimethyl trans-3-(4-bromo­phen­yl)-2-methyl­isoxazolidine-4,5-dicarboxyl­ate

Abstract

In the title compound, C14H16BrNO5, the isoxazolidine ring adopts an envelope conformation, with the N atom at the flap. In the crystal, inter­molecular C—H(...)N and C—H(...)O hydrogen bonds generate R 3 3(18) ring motifs which are fused into a ribbon-like structure extending along the b axis.

Related literature

For general background, see: Confalone & Huie (1988 [triangle]); Torssell (1988 [triangle]); Frederickson (1997 [triangle]); Gothelf & Jorgensen (1998 [triangle]); Chiacchio et al. (2003 [triangle]); Padwa et al. (1981 [triangle], 1984 [triangle]); Ochiai et al. (1967 [triangle]); Baldwin & Aube (1987 [triangle]); Heaney et al. (2001 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]); Etter (1990 [triangle]). For ring conformations, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2207-scheme1.jpg

Experimental

Crystal data

  • C14H16BrNO5
  • M r = 358.19
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2207-efi6.jpg
  • a = 10.9020 (4) Å
  • b = 8.1780 (3) Å
  • c = 17.8127 (8) Å
  • β = 101.622 (3)°
  • V = 1555.56 (11) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 2.67 mm−1
  • T = 296 K
  • 0.71 × 0.60 × 0.45 mm

Data collection

  • Stoe IPDS II diffractometer
  • Absorption correction: integration (X-RED32; Stoe & Cie, 2002 [triangle]) T min = 0.327, T max = 0.480
  • 15678 measured reflections
  • 3232 independent reflections
  • 2696 reflections with I > 2σ(I)
  • R int = 0.043

Refinement

  • R[F 2 > 2σ(F 2)] = 0.044
  • wR(F 2) = 0.101
  • S = 1.12
  • 3232 reflections
  • 193 parameters
  • H-atom parameters constrained
  • Δρmax = 0.49 e Å−3
  • Δρmin = −0.93 e Å−3

Data collection: X-AREA (Stoe & Cie, 2002 [triangle]); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809032462/ci2876sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809032462/ci2876Isup2.hkl

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

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS II diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

Comment

The 1,3-dipolar cycloaddition of nitrones and alkenes is a powerful synthetic device that allows up to three new stereogenic centers to be assembled in a stereospecific manner in a single step (Confalone & Huie, 1988; Torssell, 1988; Frederickson, 1997; Gothelf & Jorgensen, 1998). Among these N and O containing five-membered heterocycles, isoxazolidines and isoxazoline derivatives have emerged as important candidates and have been shown to display useful anticancer and antiviral properties (Chiacchio et al., 2003).

The syntheses of isoxazolidine derivatives is an important subject in organic chemistry because they are found in the structure of most natural compounds and drugs. In recent years, isoxazolidine derivatives have been synthesized in high yield via intermolecular cycloaddition of N-methylnitrone with disubstituted olefins and are employed for biological evaluation.

These isoxazolidines are used in the syntheses of β-lactams (Padwa et al., 1981) which are of value in the treatment of bacterial infections (Ochiai et al., 1967), occur as natural products (Baldwin & Aube, 1987), serve as versatile synthetic intermediates (Padwa et al., 1984), and are biologically interesting compounds. In view of the interest shown in these compounds, we report herein the crystal structure of the title compound, (I).

The overall view and atom-labelling of the molecule of (I) are displayed in Fig. 1. The isoxazolidine ring (O1/N1/C7-C9) adopts an envelope conformation, with atom N1 displaced by 0.326 (2) Å from the plane of the other ring atoms (Cremer & Pople, 1975).

The crystal packing is stabilized by intermolecular C—H···N and C—H···O hydrogen bonds (Table 1). As shown in Fig. 2, these hydrogen bonds form R33(18) motifs which are fused to form ribbon-like structure extending along the b axis.

Experimental

N-Methyl-C-(4-bromophenyl)nitrone was prepared from 4-bromo benzaldehyde, N-methyl-hydroxylamine hydrochloride and sodium carbonate in CH2Cl2 according to the literature method (Heaney et al., 2001). For the preparation of the title compound, N-methyl-C-(4-bromophenyl) nitrone (453 mg, 3 mmol) and dimethylmaleate (475 mg, 3,3 mmol) were dissolved in benzene (50 ml). The reaction mixture was refluxed for 9 h, and monitored by TLC. After evaporation of the solvent, the reaction mixture was separated by column chromatography, using a mixture of hexane-ethyl acetate (1:2) as the eluent. The trans-isomer was recrystallized from methanol in 3 d (m.p. 354–355 K).

Refinement

H atoms were positioned geometrically (C-H = 0.93–0.98 Å) and refined using a riding model with Uiso(H) = 1.2Ueq(C) and 1.5Ueq(methyl C). A rotating–group model was used for the methyl groups.

Figures

Fig. 1.
A view of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
Fig. 2.
Part of the crystal structure of (I), showing the formation of hydrogen-bonded R33(18) motifs. H atoms not involved in hydrogen bonds have been omitted for clarity. Dashed lines indicate hydrogen bonds. [Symmetry codes: (i) x, 1 + y, z; (ii) 1 - x, 1/2 ...
Fig. 3.
Preparation of the title compound.

Crystal data

C14H16BrNO5F(000) = 728
Mr = 358.19Dx = 1.529 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 15678 reflections
a = 10.9020 (4) Åθ = 1.9–28.0°
b = 8.1780 (3) ŵ = 2.67 mm1
c = 17.8127 (8) ÅT = 296 K
β = 101.622 (3)°Block, colourless
V = 1555.56 (11) Å30.71 × 0.60 × 0.45 mm
Z = 4

Data collection

Stoe IPDS II diffractometer3232 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus2696 reflections with I > 2σ(I)
plane graphiteRint = 0.043
Detector resolution: 6.67 pixels mm-1θmax = 26.5°, θmin = 1.9°
ω–scan rotation methodh = −13→13
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)k = −10→10
Tmin = 0.327, Tmax = 0.480l = −22→22
15678 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.101H-atom parameters constrained
S = 1.12w = 1/[σ2(Fo2) + (0.0399P)2 + 1.0321P] where P = (Fo2 + 2Fc2)/3
3232 reflections(Δ/σ)max = 0.001
193 parametersΔρmax = 0.49 e Å3
0 restraintsΔρmin = −0.93 e Å3

Special details

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)

xyzUiso*/Ueq
C20.4201 (3)0.5503 (4)0.18030 (16)0.0460 (7)
H20.41490.49780.22590.055*
C80.1314 (2)0.4572 (3)0.16330 (15)0.0371 (5)
H80.17540.52070.20720.044*
C50.4354 (3)0.7096 (5)0.04589 (18)0.0617 (9)
H50.43990.76420.00070.074*
C120.0010 (4)0.8290 (4)0.0637 (3)0.0793 (12)
H12C0.03110.93800.07610.095*
H12B−0.08500.82160.06850.095*
H12A0.00740.80370.01200.095*
C110.0347 (3)0.5632 (3)0.11402 (16)0.0403 (6)
O30.0753 (2)0.7144 (3)0.11549 (15)0.0625 (6)
C100.3202 (3)0.1297 (5)0.1037 (2)0.0643 (9)
H10C0.39900.17230.09650.077*
H10B0.26420.11920.05490.077*
H10A0.33290.02430.12780.077*
C40.5204 (3)0.7411 (4)0.11187 (18)0.0473 (7)
C60.3420 (3)0.5947 (5)0.04732 (18)0.0575 (8)
H60.28440.57150.00250.069*
N10.2659 (2)0.2410 (3)0.15238 (14)0.0448 (5)
O10.14367 (19)0.1690 (2)0.15537 (13)0.0506 (5)
O2−0.0615 (2)0.5161 (3)0.07465 (15)0.0670 (7)
C13−0.0534 (3)0.2653 (4)0.17647 (19)0.0497 (7)
C14−0.2378 (3)0.3749 (6)0.2055 (3)0.0783 (12)
H14C−0.26370.45660.23780.094*
H14B−0.26670.26960.21830.094*
H14A−0.27280.39940.15290.094*
O4−0.1095 (2)0.1619 (3)0.1377 (2)0.0846 (9)
O5−0.1029 (2)0.3738 (3)0.21707 (14)0.0628 (6)
Br10.64870 (3)0.89981 (5)0.11195 (2)0.06568 (15)
C30.5147 (3)0.6630 (4)0.17970 (17)0.0462 (7)
H30.57320.68570.22420.055*
C70.2260 (2)0.3988 (3)0.11494 (15)0.0385 (6)
H70.18170.37880.06220.046*
C90.0865 (3)0.2939 (4)0.19170 (16)0.0432 (6)
H90.11850.28630.24710.052*
C10.3332 (2)0.5142 (4)0.11427 (15)0.0400 (6)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C20.0426 (14)0.0554 (18)0.0379 (14)−0.0027 (13)0.0028 (12)0.0067 (13)
C80.0342 (12)0.0394 (14)0.0357 (13)−0.0002 (11)0.0024 (11)−0.0037 (11)
C50.0592 (19)0.082 (3)0.0438 (17)−0.0175 (18)0.0108 (15)0.0108 (17)
C120.089 (3)0.0383 (18)0.097 (3)0.0084 (18)−0.013 (2)0.005 (2)
C110.0381 (13)0.0392 (15)0.0430 (14)0.0014 (11)0.0070 (12)−0.0011 (12)
O30.0635 (14)0.0341 (11)0.0769 (15)−0.0017 (10)−0.0164 (12)−0.0014 (11)
C100.060 (2)0.061 (2)0.075 (2)0.0151 (17)0.0198 (18)−0.0072 (18)
C40.0387 (14)0.0532 (17)0.0517 (17)−0.0047 (13)0.0135 (13)−0.0030 (14)
C60.0530 (17)0.081 (2)0.0361 (15)−0.0153 (17)0.0021 (13)0.0038 (16)
N10.0378 (11)0.0448 (14)0.0520 (14)0.0067 (10)0.0094 (11)0.0022 (11)
O10.0472 (11)0.0391 (11)0.0675 (14)0.0010 (9)0.0162 (10)0.0016 (10)
O20.0493 (12)0.0642 (16)0.0749 (16)−0.0133 (11)−0.0174 (12)0.0165 (13)
C130.0463 (16)0.0454 (17)0.0604 (18)0.0012 (14)0.0176 (15)0.0068 (15)
C140.0518 (19)0.094 (3)0.095 (3)0.012 (2)0.030 (2)0.002 (2)
O40.0544 (14)0.0595 (16)0.142 (3)−0.0144 (12)0.0256 (17)−0.0311 (18)
O50.0482 (12)0.0809 (17)0.0622 (14)0.0056 (11)0.0182 (11)−0.0075 (12)
Br10.0557 (2)0.0767 (3)0.0680 (2)−0.02186 (17)0.02031 (16)0.00019 (19)
C30.0383 (14)0.0518 (17)0.0452 (15)−0.0021 (12)0.0007 (12)−0.0004 (14)
C70.0352 (12)0.0441 (15)0.0345 (13)0.0012 (11)0.0026 (10)0.0000 (12)
C90.0434 (14)0.0454 (16)0.0414 (14)0.0032 (12)0.0102 (12)0.0049 (13)
C10.0352 (13)0.0477 (16)0.0361 (13)0.0005 (12)0.0046 (11)0.0011 (12)

Geometric parameters (Å, °)

C2—C31.385 (4)C10—H10A0.96
C2—C11.386 (4)C4—C31.379 (4)
C2—H20.93C4—Br11.908 (3)
C8—C111.503 (4)C6—C11.382 (4)
C8—C91.542 (4)C6—H60.93
C8—C71.547 (3)N1—O11.468 (3)
C8—H80.98N1—C71.478 (4)
C5—C41.367 (5)O1—C91.419 (3)
C5—C61.390 (5)C13—O41.181 (4)
C5—H50.93C13—O51.326 (4)
C12—O31.444 (4)C13—C91.512 (4)
C12—H12C0.96C14—O51.444 (4)
C12—H12B0.96C14—H14C0.96
C12—H12A0.96C14—H14B0.96
C11—O21.202 (4)C14—H14A0.96
C11—O31.312 (4)C3—H30.93
C10—N11.462 (4)C7—C11.505 (4)
C10—H10C0.96C7—H70.98
C10—H10B0.96C9—H90.98
C3—C2—C1121.2 (3)C5—C6—H6119.5
C3—C2—H2119.4C10—N1—O1104.5 (2)
C1—C2—H2119.4C10—N1—C7113.2 (2)
C11—C8—C9117.3 (2)O1—N1—C7100.31 (19)
C11—C8—C7108.7 (2)C9—O1—N1102.4 (2)
C9—C8—C7101.9 (2)O4—C13—O5125.3 (3)
C11—C8—H8109.5O4—C13—C9126.9 (3)
C9—C8—H8109.5O5—C13—C9107.7 (3)
C7—C8—H8109.5O5—C14—H14C109.5
C4—C5—C6119.0 (3)O5—C14—H14B109.5
C4—C5—H5120.5H14C—C14—H14B109.5
C6—C5—H5120.5O5—C14—H14A109.5
O3—C12—H12C109.5H14C—C14—H14A109.5
O3—C12—H12B109.5H14B—C14—H14A109.5
H12C—C12—H12B109.5C13—O5—C14116.2 (3)
O3—C12—H12A109.5C4—C3—C2118.7 (3)
H12C—C12—H12A109.5C4—C3—H3120.6
H12B—C12—H12A109.5C2—C3—H3120.6
O2—C11—O3124.4 (3)N1—C7—C1113.1 (2)
O2—C11—C8125.7 (3)N1—C7—C8100.8 (2)
O3—C11—C8109.8 (2)C1—C7—C8114.6 (2)
C11—O3—C12117.1 (3)N1—C7—H7109.3
N1—C10—H10C109.5C1—C7—H7109.3
N1—C10—H10B109.5C8—C7—H7109.3
H10C—C10—H10B109.5O1—C9—C13109.1 (2)
N1—C10—H10A109.5O1—C9—C8106.0 (2)
H10C—C10—H10A109.5C13—C9—C8116.8 (2)
H10B—C10—H10A109.5O1—C9—H9108.2
C5—C4—C3121.5 (3)C13—C9—H9108.2
C5—C4—Br1120.0 (2)C8—C9—H9108.2
C3—C4—Br1118.5 (2)C6—C1—C2118.5 (3)
C1—C6—C5121.1 (3)C6—C1—C7119.6 (3)
C1—C6—H6119.5C2—C1—C7121.8 (2)
C9—C8—C11—O2−25.5 (4)C9—C8—C7—N1−26.7 (2)
C7—C8—C11—O289.3 (3)C11—C8—C7—C187.0 (3)
C9—C8—C11—O3159.4 (2)C9—C8—C7—C1−148.5 (2)
C7—C8—C11—O3−85.8 (3)N1—O1—C9—C13161.6 (2)
O2—C11—O3—C12−2.7 (5)N1—O1—C9—C835.1 (3)
C8—C11—O3—C12172.4 (3)O4—C13—C9—O1−3.5 (5)
C6—C5—C4—C3−0.8 (5)O5—C13—C9—O1174.0 (2)
C6—C5—C4—Br1−179.4 (3)O4—C13—C9—C8116.5 (4)
C4—C5—C6—C10.8 (6)O5—C13—C9—C8−65.9 (3)
C10—N1—O1—C9−170.5 (2)C11—C8—C9—O1113.7 (3)
C7—N1—O1—C9−53.0 (2)C7—C8—C9—O1−4.9 (3)
O4—C13—O5—C14−7.2 (5)C11—C8—C9—C13−8.0 (4)
C9—C13—O5—C14175.2 (3)C7—C8—C9—C13−126.6 (3)
C5—C4—C3—C20.0 (5)C5—C6—C1—C2−0.2 (5)
Br1—C4—C3—C2178.6 (2)C5—C6—C1—C7176.0 (3)
C1—C2—C3—C40.7 (5)C3—C2—C1—C6−0.6 (5)
C10—N1—C7—C1−77.9 (3)C3—C2—C1—C7−176.7 (3)
O1—N1—C7—C1171.2 (2)N1—C7—C1—C6133.1 (3)
C10—N1—C7—C8159.2 (2)C8—C7—C1—C6−112.1 (3)
O1—N1—C7—C848.3 (2)N1—C7—C1—C2−50.9 (4)
C11—C8—C7—N1−151.2 (2)C8—C7—C1—C263.9 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C3—H3···N1i0.932.563.492 (4)179
C12—H12C···O1ii0.962.523.434 (5)158

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x, y+1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CI2876).

References

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