5-Benzyl-7-methyl­hexa­hydro-3a,7-methano-1H-furo[3,4-c]azocine-3,10(4H)-dione

Zhan-Kun Yang; Feng-Peng Wang

doi:10.1107/S160053681100300X

. 2011 Feb 5;67(Pt 3):o577. doi: 10.1107/S160053681100300X

5-Benzyl-7-methylhexahydro-3a,7-methano-1H-furo[3,4-c]azocine-3,10(4H)-dione

Zhan-Kun Yang ^a, Feng-Peng Wang ^a,^*

PMCID: PMC3051963 PMID: 21522339

Abstract

The title compound, C₁₈H₂₁NO₃, was obtained via a double Mannich condensation reaction of 6-methyltetrahydroisobenzofuran-1,7(3H,7aH)-dione with formaldehyde and benzylamine. The molecule contains three fused rings of which the cyclohexanone and piperidine rings adopt chair conformations and the furanone ring assumes an envelope conformation. An intermolecular C—H⋯π interaction is present in the crystal structure.

Related literature

For the double Mannich condensation reaction, see: Guthmann et al. (2009 ▶); Coates et al. (1994 ▶); Barker et al. (2002 ▶). For the methylation of the β-keto ester in the synthesis of the title compound, see: Weiler (1970 ▶).

Experimental

Crystal data

C₁₈H₂₁NO₃
M _r = 299.36
Orthorhombic,
a = 10.795 (2) Å
b = 14.386 (3) Å
c = 9.797 (2) Å
V = 1521.5 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.20 × 0.20 × 0.20 mm

Data collection

Rigaku Saturn 724 diffractometer
10268 measured reflections
1584 independent reflections
1546 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.067
wR(F ²) = 0.167
S = 1.16
1584 reflections
200 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; 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: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681100300X/xu5143sup1.cif

e-67-0o577-sup1.cif^{(21.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681100300X/xu5143Isup2.hkl

e-67-0o577-Isup2.hkl^{(78.1KB, hkl)}

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

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

Cg is the centroid of the phenyl ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8B⋯Cgⁱ	0.97	2.87	3.833 (6)	169

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Symmetry code: (i) Inline graphic .

Acknowledgments

The work was supported by the National Natural Science Foundation of China (grant No. 30873147).

supplementary crystallographic information

Comment

The AE rings of diterpenoid alkaloids have received much attention as key intermediate in the total syntheses of diterpenoid alkaloids. Double Mannich condensation (Guthmann et al., 2009; Coates et al., 1994; Barker et al., 2002) is an efficient method to append the E ring to the A ring. Therefore, we have designed and synthesized the racemic 1-substituted AE-bicyclic analogue by double Mannich condensation. Herein, we report the structure of the title compound.

As illustrated in Fig. 1, the molecule of the title compound is constructed from the fusion of a cyclohexanone ring, a piperidine ring and a furanone ring. The two six-membered rings are in standard chair conformations. The furanone ring is cis-fused with the cyclohexanone ring and adopts envelope conformation. The bond angles around C4 and C5 are indicative of sp² hybridization for the two atoms. And the strain in the furanone ring is illustrated by the much distorted triangular geometry of C4 atom and the bond angles around C4 range between 109.7 (4) and 128.6 (5)°.

Experimental

The intermediate, 6-methyltetrahydroisobenzofuran-1,7(3H,7aH)-dione (1b), was synthesized according to the procedure described by Weiler (1970). A solution of tetrahydroisobenzofuran-1,7(3H,7aH)-dione (1.00 g, 6.49 mmol) in THF (10 mL) was added to 1M lithium diisopropylamide solution in THF (14.2 ml, 14.2 mmol) at 273 K. After 30 min, CH₃I (0.48 ml, 7.71 mmol) was added dropwise in the mixture. Then the mixture was stirred at the same temperature for 2 h. H₂O (20 mL) was added and the solution was extracted with CH₂Cl₂ (60 mL). The organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography (ethyl acetate/hexane, v:v, 1:2) to give 1b. (0.382 g, yield 35%) as a colourless oil.

To a solution of 1b (200 mg, 1.19 mmol) in EtOH (300 mL) was added 37% CH₂O solution (0.29 mL, 3.57 mmol) and phenylmethanamine (195 µL, 1.79 mmol). The reaction mixture was refluxing for 48 h and then concentrated under reduced pressure. The crude product was purified by flash column chromatography (ethyl acetate/hexane, v:v, 1:4) to give the title compound (107 mg, yield 30%) as a white solid. Crystallization from a ethyl acetate-petroleum ether system yielded colourless crystals suitable for single-crystal structure determination.