9-{[4-(Dimethyl­amino)­benz­yl]amino}-5-(3,4,5-trimeth­oxy­phen­yl)-5,5a,8a,9-tetra­hydro­furo[3′,4′:6,7]naphtho­[2,3-d][1,3]dioxol-6(8H)-one

Yan Li; Huo Wang; Hong Chen; Li-Ting Chen; Jing Liu

doi:10.1107/S1600536811019234

. 2011 May 28;67(Pt 6):o1538–o1539. doi: 10.1107/S1600536811019234

9-{[4-(Dimethylamino)benzyl]amino}-5-(3,4,5-trimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one

Yan Li ^a,^*, Huo Wang ^b, Hong Chen ^c,^d, Li-Ting Chen ^d, Jing Liu ^d

PMCID: PMC3120627 PMID: 21754898

Abstract

In the title compound, C₃₁H₃₄N₂O₇, the fused tetrahydrofuran and six-membered rings each display an envelope conformation. The dihedral angles between the benzene ring of the benzo[d][1,3]dioxole and the other two benzene rings are 89.68 (3) and 63.38 (2)°. In the crystal, weak intermolecular C—H⋯O hydrogen bonds link the molecules.

Related literature

For details of the synthesis and biological activity of podophyllotoxin (systematic name (10R,11R,15R,16R)-16-hydroxy-10-(3,4,5-trimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.03,7.011,15]hexadeca-1,3(7),8-trien-12-one) derivatives, see: Yu et al. (2008 ▶); Zhao et al. (2009 ▶); Lu et al. (2010 ▶). For related structures, see: Zhang et al. (1994 ▶); Feng et al. (2008 ▶); Zuo et al. (2009 ▶).

Experimental

Crystal data

C₃₁H₃₄N₂O₇
M _r = 546.60
Monoclinic,
a = 10.188 (2) Å
b = 11.530 (3) Å
c = 11.691 (3) Å
β = 96.192 (4)°
V = 1365.4 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.12 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2007 ▶) T _min = 0.981, T _max = 0.989
17611 measured reflections
6335 independent reflections
4878 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.061
S = 1.02
6335 reflections
370 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2007 ▶); 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: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811019234/cv5091sup1.cif

e-67-o1538-sup1.cif^{(28KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811019234/cv5091Isup2.hkl

e-67-o1538-Isup2.hkl^{(310KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811019234/cv5091Isup3.cml

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
C1—H1B⋯O6ⁱ	0.99	2.38	3.2904 (16)	153
C21—H21A⋯O6ⁱⁱ	0.98	2.51	3.3662 (18)	145
C22—H22B⋯O3ⁱⁱⁱ	0.98	2.54	3.4909 (18)	162
C29—H29C⋯O1^iv	0.98	2.49	3.3017 (18)	140

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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant No. 30873363), the Program of the Science Foundation of Tianjin (08JCYBJC070000) and the Major Program of the Science Foundation of Tianjin (09ZCKFSH01700).

supplementary crystallographic information

Comment

Podophyllotoxin and its derivatives are well known as substances with anti-cancer activity. In our group, we synthesize different kinds of Podophyllotoxin compounds in the search for new derivatives with improved bioactivities (Lu et al., 2010; Yu et al., 2008; Zhao et al., 2009). In this paper, we present the crystal structure of the title compound (I).

In (I) (Fig. 1),the bond lengths and angles are normal and in a good agreement with those reported previously for related compounds (Feng et al., 2008; Zhang et al., 1994; Zuo et al., 2009). The tetrahydrofuran ring (C6—C9/O3) and the six-membered ring (C4—C6/C9—C11) fused to it both display envelope conformations. The dihedral angles between the benzene ring (C2—C4/C11—C13) of the benzo[d]-[1,3]dioxole and the other two benzene ring (C23—C88 and C15—C20) are 89.68 (3) and 63.38 (2) °, respectively.

Weak intermolecular C—H···O interactions (Table 1) stabilize the crystal packing.

Experimental

The target compound was synthesized in two steps. 4-(Dimethylamino)benzaldehyde, 4β-amino podophyllotoxin, two drops of acetic acid in 95% ethanol was stirred for 6 h. Appropriate amount of NaBH₄ was added into the reaction mixture to stirred for 1 h at 273 K. Then add 5% HCl to end off the reaction, the reaction mixture was concentrated in vacuo. Add saturated NaHCO₃ to adjust PH>7. The reaction mixture was extracted with CH₂Cl₂ and dried over MgSO₄ and concentrated in vacuo. The residue was resolved in a methanol solution and slow evaporation over two weeks at room temperature gave transparent crystals suitable for X-ray analysis.