7-Methyl-9-p-tolyl-4,9-dihydro­furo[3,4-b]quinolin-1(3H)-one

Chunling Shi; Min Ji

doi:10.1107/S1600536808041457

. 2008 Dec 13;65(Pt 1):o100. doi: 10.1107/S1600536808041457

7-Methyl-9-p-tolyl-4,9-dihydrofuro[3,4-b]quinolin-1(3H)-one

Chunling Shi ^a,^*, Min Ji ^a

PMCID: PMC2968025 PMID: 21581564

Abstract

In the title compound, C₁₉H₁₇NO₂, the dihydropyridine ring adopts a flattened boat conformation while the furanone ring is almost planar (r.m.s. deviation 0.018 Å). The molecules are linked into chains along the b axis by N—H⋯O intermolecular hydrogen bonds. In addition, C—H⋯π interactions involving the phenyl ring of the tolyl group as π acceptor are observed.

Related literature

For the biological activities of podophyllotoxin and its derivatives, see: Bosmans et al. (1989 ▶); Eycken et al. (1989 ▶); Hitosuyanagi et al. (1997 ▶, 1999 ▶); Lienard et al. (1991 ▶); Magedov et al. (2007 ▶); Poli & Giambastiani (2002 ▶); Tomioka et al. (1989 ▶, 1993 ▶); Tratrat et al. (2002 ▶).

Experimental

Crystal data

C₁₉H₁₇NO₂
M _r = 291.34
Monoclinic,
a = 9.178 (2) Å
b = 11.457 (2) Å
c = 14.350 (4) Å
β = 103.124 (5)°
V = 1469.5 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 223 (2) K
0.60 × 0.48 × 0.45 mm

Data collection

Rigaku Mercury diffractometer
Absorption correction: multi-scan (Jacobson, 1998 ▶) T _min = 0.756, T _max = 0.962
13947 measured reflections
2675 independent reflections
2364 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.135
S = 1.16
2675 reflections
202 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrystalClear (Rigaku, 2000 ▶); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2003 ▶); 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 global, I. DOI: 10.1107/S1600536808041457/ci2738sup1.cif

e-65-0o100-sup1.cif^{(19.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808041457/ci2738Isup2.hkl

e-65-0o100-Isup2.hkl^{(131.4KB, 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
N1—H1⋯O2ⁱ	0.87	2.11	2.862 (2)	144
C19—H19A⋯Cg1ⁱⁱ	0.97	2.69	3.645 (3)	167

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Symmetry codes: (i) Inline graphic ; (ii) . Cg1 is centroid of the C13–C18 ring.

Acknowledgments

The authors are grateful to the Foundation of the Key Laboratory of Biotechnology of Medical Plants of Jiangsu Province for financial support.

supplementary crystallographic information

Comment

Podophyllotoxin is an antitumor lignan that inhibits microtubule assembly (Eycken et al., 1989; Tomioka et al., 1989; Bosmans et al., 1989). Because of mostly unsuccessfull attempts to use it for the treatment of human neoplasia and complicated side effects, extensive structural modifications have been performed in order to obtain more potent and less toxic anticancer agents (Tomioka et al., 1993; Lienard et al., 1991; Poli et al., 2002). Among them, 4-aza-podophyllotoxin (9-aryl-4,9-dihydrofuro [3,4-b]quinolin-1(3H)-one) derivatives reported as powerful DNA topoisomerase II inhibitors, have recently attached considerable interest (Hitosuyanagi et al., 1997; Hitosuyanagi et al., 1999; Tratrat et al., 2002; Magedov et al., 2007). We report here the crystal structure of the title compound, which was synthesized by the three-component reaction of 4-methylaniline with 4-methylbenzaldehyde and tetronic acid catalyzed by L-proline using ethanol as solvent at 353 K.

In the title compound, the dihydropyridine ring (C1-C5/N1) adopts a flattened boat conformation, with atoms C3 and N1 deviating from the C1/C2/C4/C5 plane (r.m.s. deviation 0.009 Å) by 0.102 (3) and 0.050 (3) Å, respectively (Fig. 1). The five-membered ring is almost planar (r.m.s. deviation 0.018 Å). The dihedral angle between C1/C2/C6/C7-C9 and C1/C2/C4/C5 planes is 2.9 (1)° and that between C1/C2/C4/C5 and C13-C18 plane is 79.77 (7)°.

The molecules are linked into chains (Fig.2) along the b axis by N—H···O intermolecular hydrogen bonds (Table 1). In addition, C—H···π interactions involving the phenyl ring of the tolyl group are observed.

Experimental

The title compound was prepared by the reaction of 4-methylaniline (1 mmol) and 4-methylbenzaldehyde (1 mmol) with tetronic acid (1 mmol) in the presence of L-proline (0.1 mmol) in ethanol (2 ml) at 353 K. Crystals of the title compound suitable for X-ray diffraction were obtained by slow evaporation of a N,N-dimethylformamide and ethanol solution. ¹H NMR (DMSO-d₆, δ): 2.12 (3H, s, CH₃), 2.22 (3H, s, CH₃), 4.85 (1H, d, J = 16.0 Hz, CH), 4.91 (1H, s, CH), 4.94 (1H, d, J = 16.0 Hz, CH), 6.80–6.84 (2H, m, ArH), 6.93 (1H, d, J = 8.0 Hz, ArH), 7.04–7.08 (4H, m, ArH), 9.94 (1H, s, NH).