2,5-Dimethyl-3-(3-methyl­thio­phen-2-yl)perhydro­pyrrolo[3,4-d]isoxazole-4,6-dione

Mustafa Odabaşoğlu; Hamdi Özkan; Yılmaz Yıldırır; Orhan Büyükgüngör

doi:10.1107/S1600536808012993

. 2008 May 17;64(Pt 6):o1102–o1103. doi: 10.1107/S1600536808012993

2,5-Dimethyl-3-(3-methylthiophen-2-yl)perhydropyrrolo[3,4-d]isoxazole-4,6-dione

Mustafa Odabaşoğlu ^a, Hamdi Özkan ^b, Yılmaz Yıldırır ^b, Orhan Büyükgüngör ^c,^*

PMCID: PMC2961365 PMID: 21202616

Abstract

The crystal structure of the title compound, C₁₂H₁₄N₂O₃S, exhibits intramolecular C—H⋯S and intermolecular C—H⋯S, C—H⋯O hydrogen bonds, C—S⋯N [S⋯N = 2.980 (2) Å, C—S⋯N = 145.78 (17)°] and C—H⋯π interactions; these interactions generate two C(5) chains and S(4), S(6) and R ₄ ⁴(28) ring motifs. The isoxazole ring has an envelope conformation; the N atom, which is the flap atom, is displaced by 0.261 (2) Å from the plane defined by the remaining four atoms. The dihedral angle between the succinimide and thiophene rings is 46.8 (2)°.

Related literature

For general background, see: Huisgen (1960 ▶); Black et al. (1975 ▶); Alibes et al. (2003 ▶); Kumar et al. (2003 ▶); Richman (2001 ▶); Chiacchio et al. (2003a ▶,b ▶). For ring motif details, see: Etter (1990 ▶); Bernstein et al. (1995 ▶). For related literature, see: Malamidou-Xenikaki et al. (1997 ▶); Coutouli-Argyropoulou et al. (1997 ▶); De Clercq (2002a ▶,b ▶,c ▶).

Experimental

Crystal data

C₁₂H₁₄N₂O₃S
M _r = 266.31
Orthorhombic,
a = 12.0318 (10) Å
b = 14.6759 (9) Å
c = 7.2635 (4) Å
V = 1282.57 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 296 (2) K
0.52 × 0.48 × 0.43 mm

Data collection

STOE IPDS2 diffractometer
Absorption correction: integration (X-RED32; Stoe & Cie, 2002 ▶) T _min = 0.895, T _max = 0.929
12725 measured reflections
2511 independent reflections
2212 reflections with I > 2σ(I)
R _int = 0.058

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.090
S = 1.08
2511 reflections
177 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.16 e Å⁻³
Absolute structure: Flack (1983 ▶), 1151 Friedel pairs
Flack parameter: 0.01 (9)

Data collection: X-AREA (Stoe & Cie, 2002 ▶); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002 ▶); 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, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808012993/gw2041sup1.cif

e-64-o1102-sup1.cif^{(18.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808012993/gw2041Isup2.hkl

e-64-o1102-Isup2.hkl^{(120.9KB, hkl)}

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—H7C⋯S1	0.96	2.97	3.467 (3)	114
C5—H5C⋯S1ⁱ	0.96	2.91	3.808 (3)	156
C8—H8⋯O3ⁱⁱ	0.88 (2)	2.56 (2)	3.426 (3)	168 (2)
C12—H12C⋯Cg1ⁱⁱⁱ	0.96	2.94	3.693 (3)	137

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 is the centroid of the S1,C1–C4 ring.

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS2 diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

Comment

A general principle for the synthesis of five-membered rings was introduced in 1960 as 1,3-dipolar cycloaddition and turned out to be remarkably widespread (Huisgen, 1960). Because of easy 1,3-dipolar cycloaddition reactions to alkenes, alkynes, isocyanates, isothiocyanates, phospharanes, sulphenes and sulphynl compounds, nitrones are the important intermediates in synthetic organic chemistry (Black et al., 1975). Especially, the nitrone-olefin 1,3-dipolar cycloaddition reaction is interesting since it can create three new contiguous stereogenic centers in a single step (Alibes et al., 2003). Both inter and intramolecular nitrone cycloaddition reactions have received attention because they are useful methods for the formation of heterocycles of biological active compounds (Kumar et al., 2003).

There has been an ever-increasing quest for modified nucleosides due to their potential applications in antiviral and anticancer therapies (Richman, 2001; De Clercq, 2002a,b,c). In a recent approach to modified nucleosides, the furanose ring has been replaced by other heterocyclic analogs (Chiacchio et al., 2003a). 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., 2003b). Consequently, synthetic studies on isoxazolidines have drawn considerable attention and 1,3-dipolar cycloadditions of nitrones afford the most straightforward route to isoxazolidines and we have described, the syntheses and crystal structure of, (I), 2,5-dimethyl-3-(3-methylthiophen-2-yl)-dihydro-2H-pyrrolo [3,4-d]isoxazole-4,6(5H,6aH)-dione.

The overall view and atom-labeling of the molecule of (I) are displayed in Figure 1. The hydrogen-bonding parameters are given in Table 1 and the packing arrangement of the molecules is illustrated in Figures 2–5. Compound is stabilized by intramolecular C—H···S hydrogen bond and S···N heteroatom interactions [in C1—S1···N; S···N = 2.980 (2) Å, C1—S1···N = 145.78 (17) °], which form S(4) and S(6) motifs, and intermolecular C—H···S and C—H···O hydrogen bonds and C—H···π interactions. As shown in Figures 2 and 3 the structure of the compound is made up of C8—H8···O3 and C5—H5c···S1 H-bonded polymeric bands of [C₁₂H₁₄N₂O₃S] molecules which are lined up nearly along the diagonal of the (100) (Fig. 2) and (001) (Fig. 3) planes. These polymeric C(5) chains are linked to each other and generate R₄⁴(28) ring motifs (Bernstein et al., 1995; Etter, 1990) (Fig. 4). The crystal packing is also stabilized by C12—H12c···Cg1 interactions (Fig. 5, Table 1). The dihedral angle between the succinimide and thiophen rings in [C₁₂ H₁₄ N₂ O₃ S] molecules is 46.8 (2) °.

Experimental

N-Methyl-C-(-3-methylthiophen)nitrone was prepared from 3-methylthiophenecarbaldehyde, N-methyl-hydroxylamine hydrochloride and sodium carbonate in ethanol according to the procedure previously described (Malamidou-Xenikaki et al., 1997). This substance (3 mmol, 0.465 g) and N-methylmaleimide (3.3 mmol, 0.370 g) was dissolved in 50 ml benzene. The reaction mixture was refluxed for 9 h monitored by TLC. After evaporation of the solvent, the reaction mixture was separated by column chromatography, using mixtures of petroleum ether and ethyl acetate (1:1) as the eluant. The cis-isomer, (I), was recrystallized from CHCl₃ / n-hexane (Fig. 6) (mp: 403–405 K).