6-Oxo-5-[(trifluoro­meth­yl)sulfon­yl]-1,2,4a,5,6,11b-hexa­hydro-1,3-dioxolo[4,5-j]phenanthridin-2-yl benzoate

Chunli Wu; Pan Li; Xiufang Shi; Xiaotao Pan; Jizhou Wu

doi:10.1107/S1600536811001085

. 2011 Jan 15;67(Pt 2):o382. doi: 10.1107/S1600536811001085

6-Oxo-5-[(trifluoromethyl)sulfonyl]-1,2,4a,5,6,11b-hexahydro-1,3-dioxolo[4,5-j]phenanthridin-2-yl benzoate

Chunli Wu ^a,^b,^*, Pan Li ^b, Xiufang Shi ^b, Xiaotao Pan ^b, Jizhou Wu ^a

PMCID: PMC3051489 PMID: 21523058

Abstract

In the title compound, C₂₂H₁₆F₃NO₇S, the two benzene rings are almost perpendicular, the dihedral angle between their mean planes being 87.1 (1)°. The terminal O atom of the benzoate moiety is disordered over two positions with site occupancies of 0.244 (15) and 0.756 (15). The crystal structure is stablized by two types of weak intermolecular C—H⋯O hydrogen bonds.

Related literature

The title compound is an unexpected product in our recent synthesis route of phenanthridones alkaloids. It shows potent inhibitory activity against the MCF-7 cells, SK—N—SH cells and SPC-A-1 cells. For details of the synthesis, see: Banwell et al. (1995 ▶); Szántó et al. (2009a ▶,b ▶); Pampin et al. (2003 ▶). For a recent study on the antitumor activity of phenanthridones alkaloids, see: Matveenko et al. (2009 ▶).

Experimental

Crystal data

C₂₂H₁₆F₃NO₇S
M _r = 495.42
Triclinic,
a = 5.3521 (5) Å
b = 15.5146 (16) Å
c = 15.5615 (14) Å
α = 114.351 (2)°
β = 95.145 (1)°
γ = 97.072 (1)°
V = 1154.07 (19) Å³
Z = 2
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 298 K
0.45 × 0.33 × 0.19 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.913, T _max = 0.962
5980 measured reflections
4008 independent reflections
2079 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.066
wR(F ²) = 0.163
S = 1.00
4008 reflections
312 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: SMART (Siemens, 1996 ▶); cell refinement: SAINT (Siemens, 1996 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811001085/zq2082sup1.cif

e-67-0o382-sup1.cif^{(23.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811001085/zq2082Isup2.hkl

e-67-0o382-Isup2.hkl^{(196.4KB, 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
C3—H3⋯O4ⁱ	0.93	2.51	3.341 (5)	149
C15—H15A⋯O2ⁱⁱ	0.97	2.48	3.202 (5)	131

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

Acknowledgments

The authors thank Hongmin Liu (Zhengzhou University) for the single-crystal data analysis.

supplementary crystallographic information

Comment

This paper shows an unexpected product of our study about synthesis and structural characterization of phenanthridones alkaloids. The title compound was obtained under Banwell modification of the Bischler-Napieralski reaction (Banwell et al., 1995) of 1-benzoyloxy-4-(methoxycarbonylamino)-5-(3,4-methylenedioxyphenyl)cyclohex-2-ene. The formation of this product is probably due to the overuse of Tf₂O (Pampin et al., 2003), which is confirmed when a smaller amount of Tf₂O is used. What makes us excited is that the unexpected product shows potent inhibitory activity (Matveenko et al., 2009) against the MCF-7 cells (IC50 = 4.46µg/ml), SK—N—SH cells (IC50 = 1.89µg/ml) and SPC-A-1 cells (IC50 = 1.35µg/ml).

In the crystal structure of the title compound, the two benzene rings are almost perpendicular, the dihedral angle between the mean planes of the rings is 87.1 (1)°. The terminal O atom of the benzoate moiety is disordered over two positions with site-occupancies of 0.244 (15) and 0.756 (15). The environment of the N atom is essentially planar, and the bond angles C1—N1—C9, C9—N1—S1 and C1—N1—S1 around the N atom are 114.8 (3), 125.4 (2) and 119.7 (2)°, respectively. The molecules are linked into a framework by means of two types of weak C—H···O hydrogen bonds linking the CH₂ group of the 1,3-dioxolane and one O atom of the sulfonyl group [H···O = 2.48 Å, C···O = 3.201 (6) Å and C—H···O = 131°] and one CH group of the C2-C7 cyclohexene ring and one O atom of the benzodioxole moiety [H···O = 2.51 Å, C···O = 3.342 (5) Å and C—H···O = 149°].

Experimental

1-Benzoyloxy-4-(methoxycarbonylamino)-5-(3,4-methylenedioxyphenyl)cyclohex-2-ene (0.46 mmol) and 4-DMAP (1.38 mmol) were dissolved in dry CH₂Cl₂ (12 ml) and cooled to 0°C. To this mixture was added a solution of triflic anhydride (3.68 mmol) in dry CH₂Cl₂ (2 ml) over a period of 15 min. The mixture was stirred overnight at ambient temperature. The reaction mixture was then washed with saturated NaHCO₃ solution, 1M hydrochloric acid and saturated NaHCO₃ solution, subsequently. The organic layer was evaporated, and the product was isolated by column chromatography on silica (eluent: petroleum ether/acetone = 5:1). Crystals suitable for X-ray analysis were grown by slow evaporation from acetone-ethanol solution at room temperature for two weeks.

¹H NMR (400 MHz, CDCl₃, ppm): 8.11–8.04 (m, 2H), 7.65–7.56 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 6.87 (s, 1H), 6.20 (dt, J = 10.6, 2.2 Hz, 1H), 6.09 (s, 2H), 6.01 (dd, J = 10.9, 0.9 Hz, 1H), 5.91 (ddd, J = 9.5, 5.5, 2.8 Hz, 1H), 4.67 (ddd, J = 10.6, 5.5, 2.7 Hz, 1H), 3.57–3.47 (m, 1H), 3.05 (dd, J = 13.5, 4.7 Hz, 1H), 1.73 (td, J = 12.9, 10.2 Hz,1H).

¹³C NMR (101 MHz, CDCl₃, ppm): 165.96, 163.58, 153.84, 147.76, 138.98, 133.38, 129.72, 129.46, 128.49, 125.65, 121.61, 109.76, 104.44, 102.54, 69.06, 63.96, 39.83, 30.84.