1′,3′,3′-Trimethyl-2,3-diphenyl-2,3-di­hydro­isoxazole-5(4H)-spiro-2′-indoline

Naoual Laghrib; Jean-Claude Daran; Rachid Fihi; Lhou Majidi; Mohamed Azrour

doi:10.1107/S1600536809002062

. 2009 Jan 23;65(Pt 2):o374. doi: 10.1107/S1600536809002062

1′,3′,3′-Trimethyl-2,3-diphenyl-2,3-dihydroisoxazole-5(4H)-spiro-2′-indoline

Naoual Laghrib ^a, Jean-Claude Daran ^b, Rachid Fihi ^a, Lhou Majidi ^a, Mohamed Azrour ^c,^*

PMCID: PMC2968171 PMID: 21581972

Abstract

Two diastereoisomers of the title compound, C₂₅H₂₆N₂O, have been prepared by cycloaddition between 1,3,3-trimethyl-2-methyleneindoline and C-phenyl-N-phenylnitrone. The stereochemistry of the major diastereoisomer, viz. S,R/R,S, is confirmed by the X-ray analysis. The oxazole and the pyrole rings have envelope conformations. The packing is stabilized by weak C—H⋯π interactions involving the phenyl ring attached to the N atom of the oxazole and the phenyl ring of the indole fragment.

Related literature

For general background, see: Alonso-Perarnau et al. (1997 ▶); Cacciarini et al. (2000 ▶); Pariera et al. (1993 ▶). For related studies, see: Daran et al. (2006 ▶); Fihi et al. (1995 ▶, 2004 ▶); Roussel et al. (2000 ▶, 2003 ▶). For the synthetic procedure, see: Brüning et al. (1973 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). graphic file with name e-65-0o374-scheme1.jpg

Experimental

Crystal data

C₂₅H₂₆N₂O
M _r = 370.48
Orthorhombic,
a = 18.0393 (18) Å
b = 8.9854 (7) Å
c = 12.3947 (9) Å
V = 2009.1 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 180 (2) K
0.48 × 0.36 × 0.28 mm

Data collection

Stoe IPDS diffractometer
Absorption correction: none
19030 measured reflections
2021 independent reflections
1581 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.105
S = 1.15
2021 reflections
256 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: IPDS (Stoe & Cie, 2000 ▶); cell refinement: IPDS; data reduction: X-RED (Stoe & Cie, 1996 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶) and ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809002062/fl2228sup1.cif

e-65-0o374-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809002062/fl2228Isup2.hkl

e-65-0o374-Isup2.hkl^{(97.4KB, hkl)}

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

Enhanced figure: interactive version of Fig. 1

Table 1. Hydrogen-bond geometry (Å, °).

Cg1is the centroid of the C21–C26 ring and Cg2 is the centroid of the C3–C8 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯Cg1ⁱ	0.95	2.89	3.735 (3)	149
C23—H23⋯Cg2ⁱⁱ	0.95	2.95	3.803 (4)	150

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

Comment

Heterocyclic spirocompounds are of interest in synthetic organic chemistry (Pariera et al., 1993; Alonso-Perarnau et al., 1997; Cacciarini et al., 2000). The cycloaddition between dipolarophiles bearing an exocyclic carbon-carbon double bond and appropriate1,3-dipoles is one of the best methods for the synthesis of bicyclic spirocompounds.

As part of our research on bicyclic spirocompounds (Fihi et al., 1995; Roussel et al., 2000, 2003; Daran et al., 2006), we reported that methylene lactones react with 1,3-dipoles with high selectivity. In a previous article (Fihi et al., 2004) we reported that 1,3-dipolar cycloaddition of arylnitriloxydes and N-Phenylarylnitrilimines to 5-chloro-2-methylene-1,3,3-trimethylindoline is regiospecific. Arylnitriloxydes reactions lead to spiroheterocyclic compounds, whereas N-phenylarylnitrilimines reactions afforded evolutives products.

We report here, the cycloaddition of C-phenyl-N-phenylnitrone (2) to 2-methylene-1,3,3-trimethylindoline (1). The reaction produced a mixture of diastereoisomers (Fig. 2). The ratio (77 / 23%) of which was evaluated by ¹HNMR (performed on the crude reaction mixture). To confirm unambiguously the structure assignment of (3) and (3'), and to establish the stereochemistry of each spiroheterocycle, an X-ray structural analyses was carried out on the major spirocompound, because the ¹H and ¹³CNMR studies did not provide unambiguous information.

The stereochemistry of the major diastereoisomer, S,R/R,S, is confirmed by the X-ray analyses (Fig. 1). The oxazole and the pyrole rings have an envelope conformation with puckering parameters Q(2)= 0.399 (3)°, φ(2)= 218.9 (5)° and Q(2)= 0.274 (3)°, φ(2)= 218.9 (7)° (Cremer & Pople, 1975). The packing is stabilized by weak C—H···π interactions involving the phenyl attached to the nitrogen of the oxazole and the phenyl of the indole fragment (Table 1: Cg1is the centroid of the C21—C26 ring and Cg2 is the centroid of the C3—C8 ring).

Experimental

2-Methylene-1,3,3-trimethylindoline (1) is a commercial product. C-phenyl, N-diphenylnitrone (2) was synthesized according to the literature procedure (Brüning et al., 1973). A solution of (2) (1 g, 6 mmol), (1) (1,12 g, 6 mmol) in ethylacetate (40 ml) was stirred at reflux for 24 h. The solvent was then evaporated under reduced pressure. The residue was crystallized from ethanol, leading to a mixture of diastereiosomers (3) and (3'). They were separated and purified by chromatography on silica gel (eluant: dichloromethane / hexane: 10 / 90). The spirocompounds were finally recrystallized from dichloromethane.