PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 March 1; 66(Pt 3): o668.
Published online 2010 February 20. doi:  10.1107/S160053681000591X
PMCID: PMC2983703

7-p-Tolyl-10,11-dihydro­benzo[h]furo[3,4-b]quinolin-8(7H)-one

Abstract

In the title compound, C22H17NO2, the fused ring system is essentially planar (r.m.s. deviation = 0.021 Å) and the dihedral angle between the dihydro­pyridine and tolyl rings is 80.98 (11)°. In the crystal, the mol­ecules are linked into chains along the b axis by inter­molecular N—H(...)O and C—H(...)O hydrogen bonds. Adjacent chains are linked by π–π inter­actions [centroid–centroid separation = 3.5748 (15) Å].

Related literature

For the biological activity of podophyllotoxin and its derivatives, see: Bosmans et al. (1989 [triangle]); Eycken et al. (1989 [triangle]); Hitosuyanagi et al. (1997 [triangle], 1999 [triangle]); Lienard et al. (1991 [triangle]); Magedov et al. (2007 [triangle]); Poli & Giambastiani (2002 [triangle]); Tomioka et al. (1989 [triangle], 1993 [triangle]); Tratrat et al. (2002 [triangle]). For a related structure, see: Shi & Ji (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o668-scheme1.jpg

Experimental

Crystal data

  • C22H17NO2
  • M r = 327.37
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o668-efi1.jpg
  • a = 10.6954 (16) Å
  • b = 13.0566 (18) Å
  • c = 12.183 (2) Å
  • β = 107.322 (3)°
  • V = 1624.1 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 223 K
  • 0.60 × 0.34 × 0.30 mm

Data collection

  • Rigaku Mercury diffractometer
  • Absorption correction: multi-scan (Jacobson, 1998 [triangle]) T min = 0.770, T max = 0.975
  • 15611 measured reflections
  • 2978 independent reflections
  • 2476 reflections with I > 2σ(I)
  • R int = 0.043

Refinement

  • R[F 2 > 2σ(F 2)] = 0.064
  • wR(F 2) = 0.138
  • S = 1.18
  • 2978 reflections
  • 228 parameters
  • H-atom parameters constrained
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.18 e Å−3

Data collection: CrystalClear (Rigaku, 2000 [triangle]); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2003 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681000591X/ci5030sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681000591X/ci5030Isup2.hkl

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

Acknowledgments

The author thanks the Scientific Research Item of Xuzhou Institute of Technology (grant No. XKY2009114) 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). 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-podophllotoxin (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 naphthalen-1-amine with 4-methylbenzaldehyde and tetronic acid catalyzed by L-proline using ethanol as solvent at 353 K.

In the title compound, the 1,4-dihydropyridine (C1–C5/N1) and furanone rings are planar (Fig. 1) and both are coplanar with the naphthalene ring system i.e the fused ring system is essentially planar (r.m.s. deviation 0.021 Å). The dihedral angle between C1–C5/N1 and C16–C21 planes is 80.98 (11)°. The conformation of the title molecule differs from that of a related molecule, 7-methyl-9-p-tolyl-4,9-dihydrofuro[3,4-b]quinolin-1(3H)-one (Shi et al., 2009).

In the crystal structure, the molecules are linked by N1—H1···O2 and C12—H12···O1 intermolecular hydrogen bonds (Table 1) to form chains (Fig. 2) along the b axis. The adjacent chains are linked through π-π interactions between O1/C14/C4/C5/C15 and C1/C2/C6-C8/C13 rings with a centroid-centroid separation of 3.5748 (15) Å.

Experimental

The title compound was prepared by the reaction of naphthalen-1-amine (1 mmol) and 4-methylbenzalhyde (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): 2.21 (3H, s, CH3), 4.98 (1H, d, J = 16.0 Hz, CH2), 5.07 (1H, d, J = 16.0 Hz, CH2), 5.13 (1H, s, CH), 7.05 (2H, d, J = 8.0 Hz, ArH), 7.12 (3H, dd, J1 = 6.4 Hz, J2 = 8.0 Hz, ArH), 7.46 (1H, d, J = 8.8 Hz, ArH), 7.51-7.55 (1H, m, ArH), 7.60-7.64 (1H, m, ArH), 7.84 (1H, d, J = 8.0 Hz, ArH), 8.21 (1H, d, J = 8.0 Hz, ArH), 10.22 (1H, s, NH).

Refinement

H atoms were placed in calculated positions [N–H = 0.87 Å and C–H = 0.94-0.99 Å] and included in the final cycles of refinement using a riding model, with Uiso(H) = 1.2-1.5 Ueq(C).

Figures

Fig. 1.
The molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
Fig. 2.
The crystal packing of the title compound.

Crystal data

C22H17NO2F(000) = 688
Mr = 327.37Dx = 1.339 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71070 Å
Hall symbol: -P 2ybcCell parameters from 5302 reflections
a = 10.6954 (16) Åθ = 3.0–25.3°
b = 13.0566 (18) ŵ = 0.09 mm1
c = 12.183 (2) ÅT = 223 K
β = 107.322 (3)°Block, colourless
V = 1624.1 (4) Å30.60 × 0.34 × 0.30 mm
Z = 4

Data collection

Rigaku Mercury diffractometer2978 independent reflections
Radiation source: fine-focus sealed tube2476 reflections with I > 2σ(I)
graphiteRint = 0.043
Detector resolution: 7.31 pixels mm-1θmax = 25.4°, θmin = 3.1°
ω scansh = −12→11
Absorption correction: multi-scan (Jacobson, 1998)k = −15→12
Tmin = 0.770, Tmax = 0.975l = −14→14
15611 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.064Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.138H-atom parameters constrained
S = 1.18w = 1/[σ2(Fo2) + (0.0503P)2 + 0.6601P] where P = (Fo2 + 2Fc2)/3
2978 reflections(Δ/σ)max = 0.001
228 parametersΔρmax = 0.22 e Å3
0 restraintsΔρmin = −0.18 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O11.04628 (16)0.87892 (12)0.19046 (14)0.0446 (4)
O21.02197 (17)0.72658 (13)0.26734 (16)0.0520 (5)
N10.88595 (17)1.05854 (13)0.32900 (16)0.0357 (5)
H10.89211.12000.30350.043*
C10.8218 (2)1.04144 (15)0.41266 (18)0.0303 (5)
C20.8127 (2)0.94420 (16)0.45353 (18)0.0321 (5)
C30.8734 (2)0.84879 (15)0.41573 (19)0.0323 (5)
H30.94550.82520.48270.039*
C40.9332 (2)0.88088 (16)0.32405 (18)0.0327 (5)
C50.9376 (2)0.97791 (16)0.28925 (19)0.0330 (5)
C60.7450 (2)0.93198 (18)0.5358 (2)0.0442 (6)
H60.73840.86610.56480.053*
C70.6888 (3)1.01196 (18)0.5748 (2)0.0481 (7)
H70.64361.00040.62910.058*
C80.6977 (2)1.11247 (17)0.5345 (2)0.0398 (6)
C90.6407 (3)1.19767 (19)0.5729 (2)0.0518 (7)
H90.59411.18780.62640.062*
C100.6521 (3)1.2934 (2)0.5338 (3)0.0570 (7)
H100.61401.34930.56050.068*
C110.7207 (3)1.30888 (18)0.4538 (2)0.0515 (7)
H110.72961.37550.42790.062*
C120.7747 (2)1.22844 (16)0.4130 (2)0.0413 (6)
H120.81891.24000.35800.050*
C130.7652 (2)1.12779 (16)0.45230 (19)0.0330 (5)
C141.0009 (2)0.81812 (18)0.2636 (2)0.0392 (6)
C151.0079 (2)0.98353 (17)0.2007 (2)0.0410 (6)
H15A0.95001.00880.12740.049*
H15B1.08461.02840.22580.049*
C160.7751 (2)0.76137 (15)0.38090 (19)0.0332 (5)
C170.7769 (2)0.68286 (17)0.4572 (2)0.0436 (6)
H170.84200.68220.52880.052*
C180.6844 (3)0.60477 (17)0.4302 (2)0.0463 (6)
H180.68750.55270.48420.056*
C190.5881 (2)0.60229 (17)0.3254 (2)0.0395 (6)
C200.5876 (2)0.68095 (17)0.2488 (2)0.0407 (6)
H200.52390.68090.17650.049*
C210.6785 (2)0.75938 (17)0.2760 (2)0.0376 (5)
H210.67470.81210.22250.045*
C220.4884 (3)0.51737 (19)0.2961 (3)0.0541 (7)
H22A0.50150.47220.36180.081*
H22B0.49850.47880.23120.081*
H22C0.40100.54640.27630.081*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0519 (10)0.0402 (9)0.0490 (10)0.0012 (7)0.0264 (9)−0.0075 (8)
O20.0626 (12)0.0345 (10)0.0664 (12)0.0061 (8)0.0305 (10)−0.0097 (8)
N10.0415 (11)0.0252 (9)0.0463 (12)0.0009 (8)0.0222 (9)0.0003 (8)
C10.0299 (11)0.0312 (12)0.0313 (12)−0.0018 (9)0.0113 (9)−0.0033 (9)
C20.0358 (12)0.0297 (12)0.0310 (12)−0.0014 (9)0.0101 (10)−0.0026 (9)
C30.0336 (12)0.0266 (11)0.0348 (12)0.0022 (8)0.0076 (10)0.0009 (9)
C40.0306 (12)0.0307 (12)0.0357 (13)−0.0018 (9)0.0084 (10)−0.0052 (9)
C50.0316 (12)0.0320 (12)0.0367 (13)−0.0003 (9)0.0119 (10)−0.0032 (9)
C60.0605 (16)0.0341 (13)0.0444 (15)−0.0012 (11)0.0254 (12)0.0034 (11)
C70.0632 (17)0.0431 (14)0.0503 (16)0.0005 (12)0.0355 (14)−0.0009 (11)
C80.0432 (14)0.0387 (13)0.0404 (13)0.0012 (10)0.0171 (11)−0.0048 (10)
C90.0601 (17)0.0476 (16)0.0573 (17)0.0051 (12)0.0321 (14)−0.0091 (12)
C100.0614 (18)0.0427 (16)0.075 (2)0.0090 (12)0.0321 (16)−0.0141 (13)
C110.0565 (16)0.0305 (13)0.0739 (19)0.0039 (11)0.0291 (14)−0.0036 (12)
C120.0426 (13)0.0309 (12)0.0540 (16)0.0001 (10)0.0198 (12)−0.0020 (11)
C130.0313 (12)0.0312 (12)0.0368 (13)−0.0018 (9)0.0108 (10)−0.0039 (9)
C140.0393 (13)0.0370 (14)0.0409 (14)−0.0001 (10)0.0114 (11)−0.0074 (10)
C150.0456 (14)0.0368 (13)0.0450 (15)−0.0006 (10)0.0201 (11)−0.0048 (10)
C160.0366 (12)0.0256 (11)0.0379 (13)0.0019 (9)0.0118 (10)−0.0013 (9)
C170.0518 (15)0.0333 (13)0.0394 (14)−0.0025 (11)0.0038 (11)0.0035 (10)
C180.0605 (16)0.0293 (12)0.0495 (16)−0.0050 (11)0.0168 (13)0.0046 (10)
C190.0372 (13)0.0318 (12)0.0523 (15)−0.0022 (9)0.0178 (11)−0.0070 (10)
C200.0358 (13)0.0414 (13)0.0410 (14)−0.0001 (10)0.0056 (10)−0.0050 (11)
C210.0418 (13)0.0320 (12)0.0383 (14)0.0018 (10)0.0109 (11)0.0027 (10)
C220.0510 (15)0.0437 (15)0.071 (2)−0.0125 (12)0.0231 (14)−0.0085 (13)

Geometric parameters (Å, °)

O1—C141.385 (3)C9—H90.94
O1—C151.442 (3)C10—C111.398 (4)
O2—C141.215 (3)C10—H100.94
N1—C51.344 (3)C11—C121.362 (3)
N1—C11.406 (3)C11—H110.94
N1—H10.87C12—C131.413 (3)
C1—C21.378 (3)C12—H120.94
C1—C131.430 (3)C15—H15A0.98
C2—C61.409 (3)C15—H15B0.98
C2—C31.538 (3)C16—C171.380 (3)
C3—C41.503 (3)C16—C211.384 (3)
C3—C161.524 (3)C17—C181.390 (3)
C3—H30.99C17—H170.94
C4—C51.341 (3)C18—C191.382 (3)
C4—C141.433 (3)C18—H180.94
C5—C151.489 (3)C19—C201.387 (3)
C6—C71.359 (3)C19—C221.506 (3)
C6—H60.94C20—C211.383 (3)
C7—C81.414 (3)C20—H200.94
C7—H70.94C21—H210.94
C8—C131.413 (3)C22—H22A0.97
C8—C91.413 (3)C22—H22B0.97
C9—C101.356 (4)C22—H22C0.97
C14—O1—C15108.88 (16)C11—C12—C13120.8 (2)
C5—N1—C1118.59 (18)C11—C12—H12119.6
C5—N1—H1120.7C13—C12—H12119.6
C1—N1—H1120.7C8—C13—C12118.4 (2)
C2—C1—N1120.70 (18)C8—C13—C1119.01 (19)
C2—C1—C13121.46 (19)C12—C13—C1122.6 (2)
N1—C1—C13117.83 (18)O2—C14—O1119.4 (2)
C1—C2—C6117.90 (19)O2—C14—C4131.3 (2)
C1—C2—C3123.82 (18)O1—C14—C4109.28 (19)
C6—C2—C3118.28 (19)O1—C15—C5103.55 (18)
C4—C3—C16114.39 (18)O1—C15—H15A111.1
C4—C3—C2107.95 (17)C5—C15—H15A111.1
C16—C3—C2111.84 (17)O1—C15—H15B111.1
C4—C3—H3107.5C5—C15—H15B111.1
C16—C3—H3107.5H15A—C15—H15B109.0
C2—C3—H3107.5C17—C16—C21117.7 (2)
C5—C4—C14107.9 (2)C17—C16—C3119.9 (2)
C5—C4—C3124.11 (19)C21—C16—C3122.32 (19)
C14—C4—C3127.9 (2)C16—C17—C18121.3 (2)
C4—C5—N1124.7 (2)C16—C17—H17119.4
C4—C5—C15110.36 (19)C18—C17—H17119.4
N1—C5—C15124.93 (19)C19—C18—C17121.2 (2)
C7—C6—C2122.4 (2)C19—C18—H18119.4
C7—C6—H6118.8C17—C18—H18119.4
C2—C6—H6118.8C18—C19—C20117.2 (2)
C6—C7—C8120.6 (2)C18—C19—C22121.2 (2)
C6—C7—H7119.7C20—C19—C22121.7 (2)
C8—C7—H7119.7C21—C20—C19121.7 (2)
C13—C8—C9119.0 (2)C21—C20—H20119.1
C13—C8—C7118.6 (2)C19—C20—H20119.1
C9—C8—C7122.4 (2)C20—C21—C16120.9 (2)
C10—C9—C8121.1 (2)C20—C21—H21119.6
C10—C9—H9119.4C16—C21—H21119.6
C8—C9—H9119.4C19—C22—H22A109.5
C9—C10—C11119.9 (2)C19—C22—H22B109.5
C9—C10—H10120.0H22A—C22—H22B109.5
C11—C10—H10120.0C19—C22—H22C109.5
C12—C11—C10120.7 (2)H22A—C22—H22C109.5
C12—C11—H11119.6H22B—C22—H22C109.5
C10—C11—H11119.6
C5—N1—C1—C20.4 (3)C9—C8—C13—C1−179.4 (2)
C5—N1—C1—C13−178.79 (19)C7—C8—C13—C10.1 (3)
N1—C1—C2—C6−178.9 (2)C11—C12—C13—C80.3 (4)
C13—C1—C2—C60.3 (3)C11—C12—C13—C1−179.3 (2)
N1—C1—C2—C31.9 (3)C2—C1—C13—C8−0.5 (3)
C13—C1—C2—C3−178.92 (19)N1—C1—C13—C8178.7 (2)
C1—C2—C3—C4−3.7 (3)C2—C1—C13—C12179.1 (2)
C6—C2—C3—C4177.1 (2)N1—C1—C13—C12−1.7 (3)
C1—C2—C3—C16−130.4 (2)C15—O1—C14—O2179.3 (2)
C6—C2—C3—C1650.4 (3)C15—O1—C14—C4−0.6 (2)
C16—C3—C4—C5128.9 (2)C5—C4—C14—O2179.8 (3)
C2—C3—C4—C53.7 (3)C3—C4—C14—O23.2 (4)
C16—C3—C4—C14−54.9 (3)C5—C4—C14—O1−0.3 (3)
C2—C3—C4—C14179.9 (2)C3—C4—C14—O1−176.95 (19)
C14—C4—C5—N1−178.8 (2)C14—O1—C15—C51.1 (2)
C3—C4—C5—N1−2.0 (4)C4—C5—C15—O1−1.3 (3)
C14—C4—C5—C151.0 (3)N1—C5—C15—O1178.54 (19)
C3—C4—C5—C15177.8 (2)C4—C3—C16—C17137.1 (2)
C1—N1—C5—C4−0.4 (3)C2—C3—C16—C17−99.8 (2)
C1—N1—C5—C15179.8 (2)C4—C3—C16—C21−45.9 (3)
C1—C2—C6—C70.4 (4)C2—C3—C16—C2177.3 (3)
C3—C2—C6—C7179.6 (2)C21—C16—C17—C18−0.5 (3)
C2—C6—C7—C8−0.8 (4)C3—C16—C17—C18176.7 (2)
C6—C7—C8—C130.5 (4)C16—C17—C18—C190.7 (4)
C6—C7—C8—C9−180.0 (2)C17—C18—C19—C20−0.1 (4)
C13—C8—C9—C10−1.3 (4)C17—C18—C19—C22179.7 (2)
C7—C8—C9—C10179.2 (3)C18—C19—C20—C21−0.7 (3)
C8—C9—C10—C110.3 (4)C22—C19—C20—C21179.5 (2)
C9—C10—C11—C121.0 (4)C19—C20—C21—C160.9 (3)
C10—C11—C12—C13−1.3 (4)C17—C16—C21—C20−0.3 (3)
C9—C8—C13—C121.0 (3)C3—C16—C21—C20−177.4 (2)
C7—C8—C13—C12−179.5 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.872.002.802 (2)153
C12—H12···O1i0.942.493.248 (3)137

Symmetry codes: (i) −x+2, y+1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CI5030).

References

  • Bosmans, J. P., Eycken, J. V. & Vandewalle, M. (1989). Tetrahedron Lett.30, 3877–3880.
  • Eycken, J. V., Bosmans, J. P., Haver, D. V. & Vandewalle, M. (1989). Tetrahedron Lett.30, 3873–3876.
  • Hitosuyanagi, Y., Kobayashi, M., Fukuyo, M., Takeya, K. & Itokawa, H. (1997). Tetrahedron Lett.38, 8295–8296.
  • Hitosuyanagi, Y., Kobayashi, M., Morita, H., Itokawa, H. & Takeya, K. (1999). Tetrahedron Lett.40, 9107–9110.
  • Jacobson, R. (1998). Private communication to the Rigaku Corporation, Tokyo, Japan.
  • Lienard, P., Royer, J., Quirion, J. C. & Husson, H. P. (1991). Tetrahedron Lett.32, 2489–2492.
  • Magedov, I. V., Manapadi, M., Rozhkova, E., Przheval’skii, N. M., Rogelj, S., Shors, S. T., Steelant, W. A., Slambrouck, S. V. & Korinienko, A. (2007). Bioorg. Med. Chem. Lett.17, 1381–1385. [PMC free article] [PubMed]
  • Poli, G. & Giambastiani, G. (2002). J. Org. Chem.67, 9456–9459. [PubMed]
  • Rigaku (2000). CrystalClear. Rigaku Corporation, Tokyo, Japan.
  • Rigaku/MSC (2003). CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Shi, C. & Ji, M. (2009). Acta Cryst. E65, o100. [PMC free article] [PubMed]
  • Tomioka, K., Kubota, Y. & Koga, K. (1989). Tetrahedron Lett.30, 2953–2954.
  • Tomioka, K., Kubota, Y. & Koga, K. (1993). Tetrahedron, 49, 1891–1900.
  • Tratrat, C., Renault, S. G. & Husson, H. P. (2002). Org. Lett.4, 3187–3189. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography