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Acta Cryst. (2009). E65, o689    [ doi:10.1107/S1600536808040749 ]

(9S,13R,14R)-7,8-Didehydro-3,4,7-trimethoxy-17-methylmorphinan-6-one

Y.-F. Li, Y. Qian, L.-H. Yin, R. Lv and H.-J. Zhu

Abstract top

The title compound, C20H25NO4, was synthesized by a Mitsunobu reaction of sinomenine [(9S,13R,14R)-7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one] with methanol. The chiral centers were unchanged during the reaction. Intramolecular C-H...O hydrogen bonds result in the formation of six-membered rings.

Comment top

(9S,13R,14R)-7,8-Didehydro-3,4,7-trimethoxy-17-methylmorphinan-6-one (I) is a derivative of natural sinomenine. Sinomenine was reported possessing anti-inflammatory, antitussive and antiarrgythmic activities (Wang et al., 1965). We report here the crystal structure of I.

The molecular structure of I is shown in Fig. 1. The X-ray diffraction results show that I is a tetracyclic alkaloid with three chiral centers. The piperidine ring is in a chair conformation, and the other two six-membered aliphatic rings are in twisted boat conformation.

The intramolecular C—H···O hydrogen bonds(C5—H5A···O1, C16—H16A···O1 and C18—H18B···O2) result in the formation of six-membered rings, which may be effective to the stabilization of the crystals.

Related literature top

For the anti-inflammatory, antitussive and antiarrgythmic activities of sinomenine, see: Wang & Li (1965).

Experimental top

(9S,13R,14R)-7,8-Didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one (5 mmol, 1.65 g), triphenyl phosphine (10 mmol, 2.62 g) and absolute methanol (1 ml) were added in tetrahydrofuran(THF, 50 ml). Diethyl azodicarboxylate(10 mmol, 1.74 g) was added in dropwise during a period of 30 min. The solution was continuosly stirred for another 12 h. The solution was concentrated under reduced pressure and the residue was purified by column chromatography on silca gel(60–100 mesh) using ethyl acetate/triethylamine (V/V = 10:1). White product was obtained by crystallization from isopropyl ether. Crystals of the product suitable for X-ray diffraction were obtained by slow evaporation of methanol solution.

Refinement top

All H atoms were positioned geometrically, with C—H=0.98, 0.97, 0.96 and 0.93 Å for methine, methylene, methyl and aromatic H atoms,respectively, and constrained to ride on their parent atoms, with Uiso(H)=xUeq(C), where x=1.5 for methyl H atoms and x=1.2 for all other H atoms. In the absence of significant anomalous dispersion effects, Friedel pairs were merged by using the instruction of "MERG 3".

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen bonds are shown as dashed lines.
(9S,13R,14S)-7,8-didehydro-3,4,7-trimethoxy-N-methyl-morphinan-6-one top
Crystal data top
C20H25NO4Dx = 1.292 Mg m−3
Mr = 343.41Mo Kα radiation, λ = 0.71073 Å
Trigonal, P32Cell parameters from 25 reflections
Hall symbol: P 32θ = 10–13°
a = 10.9590 (15) ŵ = 0.09 mm−1
c = 12.726 (3) ÅT = 298 K
V = 1323.6 (4) Å3Block, colorless
Z = 30.40 × 0.30 × 0.30 mm
F(000) = 552
Data collection top
Enraf–Nonius CAD-4
diffractometer		1281 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.037
graphiteθmax = 26.0°, θmin = 2.2°
ω/2θ scansh = −13→6
Absorption correction: ψ scan
(North et al., 1968)		k = 0→11
Tmin = 0.965, Tmax = 0.974l = −15→15
2008 measured reflections3 standard reflections every 200 reflections
1728 independent reflections intensity decay: none
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.070Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.208H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.1178P)2 + 0.4849P]
where P = (Fo2 + 2Fc2)/3
1728 reflections(Δ/σ)max = 0.005
226 parametersΔρmax = 0.45 e Å−3
44 restraintsΔρmin = −0.22 e Å−3
Crystal data top
C20H25NO4Z = 3
Mr = 343.41Mo Kα radiation
Trigonal, P32µ = 0.09 mm−1
a = 10.9590 (15) ÅT = 298 K
c = 12.726 (3) Å0.40 × 0.30 × 0.30 mm
V = 1323.6 (4) Å3
Data collection top
Enraf–Nonius CAD-4
diffractometer		1281 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.037
Tmin = 0.965, Tmax = 0.974θmax = 26.0°
2008 measured reflections3 standard reflections every 200 reflections
1728 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.070H-atom parameters constrained
wR(F2) = 0.208Δρmax = 0.45 e Å−3
S = 1.06Δρmin = −0.22 e Å−3
1728 reflectionsAbsolute structure: ?
226 parametersFlack parameter: ?
44 restraintsRogers parameter: ?
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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) top
xyzUiso*/Ueq
O10.7890 (7)0.2303 (6)0.0383 (5)0.0855 (17)
O20.8937 (7)0.0744 (5)0.1262 (6)0.093 (2)
O31.2532 (6)0.7232 (5)−0.1456 (4)0.0719 (13)
O41.0260 (6)0.4750 (6)−0.1870 (4)0.0765 (15)
N0.9014 (7)0.6779 (6)0.2458 (4)0.0607 (14)
C180.7882 (16)0.1603 (14)−0.0423 (8)0.123 (4)
H18A0.69760.1188−0.07570.185*
H18B0.80710.0873−0.02100.185*
H18C0.85950.2222−0.09090.185*
C170.9251 (11)−0.0152 (9)0.1821 (8)0.093 (3)
H17A0.8722−0.10880.15400.139*
H17B0.9009−0.01590.25470.139*
H17C1.02400.01720.17630.139*
C30.9567 (7)0.2137 (7)0.1507 (5)0.0592 (16)
C40.9072 (7)0.2945 (7)0.0963 (5)0.0563 (15)
C120.9634 (6)0.4366 (6)0.1177 (4)0.0436 (12)
C111.0594 (6)0.4957 (7)0.1981 (4)0.0470 (13)
C11.1056 (8)0.4155 (8)0.2521 (5)0.0590 (17)
H1A1.17230.45790.30510.071*
C21.0563 (8)0.2771 (8)0.2294 (6)0.0653 (19)
H2A1.08900.22590.26630.078*
C191.3723 (8)0.8546 (9)−0.1173 (7)0.082 (2)
H19A1.44850.8759−0.16460.123*
H19B1.40050.8490−0.04680.123*
H19C1.34800.9274−0.12120.123*
C200.9242 (11)0.7233 (10)0.3554 (6)0.085 (2)
H20A0.99760.82010.35940.127*
H20B0.95110.66590.39490.127*
H20C0.83880.71380.38400.127*
C150.7923 (7)0.5297 (7)0.2337 (5)0.0569 (16)
H15A0.70560.51520.26550.068*
H15B0.82130.47110.27090.068*
C160.7647 (6)0.4843 (7)0.1193 (5)0.0531 (15)
H16A0.72210.53230.08420.064*
H16B0.69940.38370.11540.064*
C130.9034 (6)0.5194 (6)0.0638 (5)0.0461 (13)
C50.8825 (7)0.4990 (7)−0.0559 (5)0.0533 (14)
H5A0.81550.4009−0.07060.064*
H5B0.84290.5550−0.08190.064*
C61.0162 (7)0.5401 (7)−0.1131 (5)0.0557 (15)
C71.1414 (7)0.6762 (7)−0.0771 (5)0.0541 (14)
C81.1330 (7)0.7371 (6)0.0109 (5)0.0532 (15)
H8A1.21190.82000.03280.064*
C141.0026 (7)0.6780 (6)0.0759 (4)0.0470 (13)
H14A0.95020.72360.05190.056*
C91.0334 (7)0.7134 (7)0.1920 (5)0.0549 (15)
H9A1.09380.81590.19660.066*
C101.1204 (8)0.6499 (7)0.2307 (5)0.0593 (16)
H10A1.12620.65620.30670.071*
H10B1.21530.70460.20310.071*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.090 (4)0.069 (3)0.099 (4)0.040 (3)−0.017 (3)−0.012 (3)
O20.101 (4)0.042 (3)0.140 (5)0.039 (3)−0.018 (4)0.016 (3)
O30.071 (3)0.068 (3)0.071 (3)0.030 (3)0.023 (2)0.011 (2)
O40.077 (3)0.081 (3)0.075 (3)0.042 (3)−0.001 (3)−0.024 (3)
N0.077 (4)0.066 (3)0.053 (3)0.046 (3)0.007 (3)0.001 (2)
C180.207 (13)0.138 (9)0.090 (7)0.135 (10)−0.005 (7)−0.001 (7)
C170.112 (7)0.062 (5)0.126 (7)0.060 (5)0.041 (6)0.043 (5)
C30.059 (4)0.051 (3)0.072 (4)0.031 (3)0.010 (3)0.020 (3)
C40.058 (4)0.041 (3)0.069 (4)0.024 (3)0.001 (3)0.014 (3)
C120.048 (3)0.046 (3)0.045 (3)0.030 (3)0.002 (2)0.010 (2)
C110.056 (3)0.055 (3)0.042 (3)0.037 (3)−0.001 (3)0.002 (2)
C10.067 (4)0.085 (5)0.049 (3)0.056 (4)−0.002 (3)0.009 (3)
C20.069 (4)0.073 (5)0.077 (4)0.053 (4)0.006 (4)0.021 (4)
C190.062 (5)0.086 (6)0.078 (5)0.023 (4)0.012 (4)−0.008 (4)
C200.124 (7)0.101 (6)0.054 (4)0.074 (6)0.010 (4)0.001 (4)
C150.061 (4)0.062 (4)0.064 (4)0.042 (3)0.010 (3)0.009 (3)
C160.045 (3)0.053 (3)0.066 (4)0.028 (3)0.002 (3)0.013 (3)
C130.047 (3)0.043 (3)0.054 (3)0.027 (3)−0.004 (3)0.006 (2)
C50.062 (3)0.046 (3)0.060 (3)0.034 (3)−0.010 (3)−0.002 (3)
C60.064 (4)0.050 (3)0.059 (3)0.032 (3)−0.002 (3)0.000 (3)
C70.060 (3)0.054 (3)0.046 (3)0.027 (3)0.004 (3)0.003 (3)
C80.058 (3)0.045 (3)0.054 (3)0.024 (3)0.003 (3)0.003 (2)
C140.060 (4)0.042 (3)0.045 (3)0.030 (3)0.004 (3)0.007 (2)
C90.065 (4)0.052 (3)0.052 (4)0.033 (3)−0.008 (3)−0.003 (3)
C100.069 (4)0.069 (4)0.048 (3)0.041 (4)−0.019 (3)−0.008 (3)
Geometric parameters (Å, °) top
O1—C181.278 (11)C19—H19B0.9600
O1—C41.344 (9)C19—H19C0.9600
O2—C31.360 (8)C20—H20A0.9600
O2—C171.388 (9)C20—H20B0.9600
O3—C71.377 (8)C20—H20C0.9600
O3—C191.424 (9)C15—C161.520 (7)
O4—C61.217 (8)C15—H15A0.9700
N—C201.461 (10)C15—H15B0.9700
N—C91.466 (9)C16—C131.541 (8)
N—C151.466 (9)C16—H16A0.9700
C18—H18A0.9600C16—H16B0.9700
C18—H18B0.9600C13—C141.528 (8)
C18—H18C0.9600C13—C51.540 (9)
C17—H17A0.9600C5—C61.490 (10)
C17—H17B0.9600C5—H5A0.9700
C17—H17C0.9600C5—H5B0.9700
C3—C21.386 (10)C6—C71.507 (9)
C3—C41.428 (8)C7—C81.330 (9)
C4—C121.385 (9)C8—C141.491 (9)
C12—C111.376 (8)C8—H8A0.9300
C12—C131.524 (7)C14—C91.523 (8)
C11—C11.395 (8)C14—H14A0.9800
C11—C101.531 (9)C9—C101.516 (9)
C1—C21.363 (10)C9—H9A0.9800
C1—H1A0.9300C10—H10A0.9700
C2—H2A0.9300C10—H10B0.9700
C19—H19A0.9600
C18—O1—C4118.1 (9)C16—C15—H15A109.1
C3—O2—C17120.6 (7)N—C15—H15B109.1
C7—O3—C19114.3 (6)C16—C15—H15B109.1
C20—N—C9112.2 (6)H15A—C15—H15B107.9
C20—N—C15112.5 (6)C15—C16—C13110.4 (5)
C9—N—C15113.3 (5)C15—C16—H16A109.6
O1—C18—H18A109.5C13—C16—H16A109.6
O1—C18—H18B109.5C15—C16—H16B109.6
H18A—C18—H18B109.5C13—C16—H16B109.6
O1—C18—H18C109.5H16A—C16—H16B108.1
H18A—C18—H18C109.5C12—C13—C14111.0 (5)
H18B—C18—H18C109.5C12—C13—C5115.9 (5)
O2—C17—H17A109.5C14—C13—C5103.5 (4)
O2—C17—H17B109.5C12—C13—C16108.0 (5)
H17A—C17—H17B109.5C14—C13—C16106.8 (5)
O2—C17—H17C109.5C5—C13—C16111.2 (5)
H17A—C17—H17C109.5C6—C5—C13112.7 (5)
H17B—C17—H17C109.5C6—C5—H5A109.0
O2—C3—C2124.0 (6)C13—C5—H5A109.0
O2—C3—C4116.6 (6)C6—C5—H5B109.0
C2—C3—C4119.2 (6)C13—C5—H5B109.0
O1—C4—C12117.9 (5)H5A—C5—H5B107.8
O1—C4—C3120.5 (6)O4—C6—C5124.2 (6)
C12—C4—C3120.6 (6)O4—C6—C7120.8 (6)
C11—C12—C4118.8 (5)C5—C6—C7115.0 (5)
C11—C12—C13120.7 (5)C8—C7—O3128.1 (6)
C4—C12—C13119.9 (5)C8—C7—C6119.7 (6)
C12—C11—C1120.2 (6)O3—C7—C6112.2 (5)
C12—C11—C10122.0 (5)C7—C8—C14122.8 (6)
C1—C11—C10117.8 (5)C7—C8—H8A118.6
C2—C1—C11122.1 (6)C14—C8—H8A118.6
C2—C1—H1A119.0C8—C14—C9112.7 (5)
C11—C1—H1A119.0C8—C14—C13114.8 (5)
C1—C2—C3119.1 (6)C9—C14—C13109.2 (5)
C1—C2—H2A120.5C8—C14—H14A106.5
C3—C2—H2A120.5C9—C14—H14A106.5
O3—C19—H19A109.5C13—C14—H14A106.5
O3—C19—H19B109.5N—C9—C10119.4 (5)
H19A—C19—H19B109.5N—C9—C14108.8 (5)
O3—C19—H19C109.5C10—C9—C14108.0 (5)
H19A—C19—H19C109.5N—C9—H9A106.7
H19B—C19—H19C109.5C10—C9—H9A106.7
N—C20—H20A109.5C14—C9—H9A106.7
N—C20—H20B109.5C9—C10—C11113.0 (5)
H20A—C20—H20B109.5C9—C10—H10A109.0
N—C20—H20C109.5C11—C10—H10A109.0
H20A—C20—H20C109.5C9—C10—H10B109.0
H20B—C20—H20C109.5C11—C10—H10B109.0
N—C15—C16112.4 (5)H10A—C10—H10B107.8
N—C15—H15A109.1
C17—O2—C3—C21.2 (12)C12—C13—C5—C6−59.6 (7)
C17—O2—C3—C4−173.7 (7)C14—C13—C5—C662.2 (6)
C18—O1—C4—C12127.8 (8)C16—C13—C5—C6176.6 (5)
C18—O1—C4—C3−64.2 (11)C13—C5—C6—O4139.7 (7)
O2—C3—C4—O111.0 (10)C13—C5—C6—C7−43.8 (7)
C2—C3—C4—O1−164.1 (7)C19—O3—C7—C8−1.0 (11)
O2—C3—C4—C12178.7 (6)C19—O3—C7—C6177.5 (6)
C2—C3—C4—C123.6 (9)O4—C6—C7—C8−172.3 (7)
O1—C4—C12—C11162.8 (6)C5—C6—C7—C811.0 (8)
C3—C4—C12—C11−5.2 (9)O4—C6—C7—O39.1 (9)
O1—C4—C12—C13−8.4 (9)C5—C6—C7—O3−167.6 (6)
C3—C4—C12—C13−176.4 (6)O3—C7—C8—C14177.1 (6)
C4—C12—C11—C14.2 (9)C6—C7—C8—C14−1.3 (9)
C13—C12—C11—C1175.3 (6)C7—C8—C14—C9150.3 (6)
C4—C12—C11—C10−176.7 (6)C7—C8—C14—C1324.5 (9)
C13—C12—C11—C10−5.6 (9)C12—C13—C14—C873.0 (6)
C12—C11—C1—C2−1.5 (10)C5—C13—C14—C8−52.0 (6)
C10—C11—C1—C2179.3 (6)C16—C13—C14—C8−169.4 (5)
C11—C1—C2—C3−0.2 (10)C12—C13—C14—C9−54.6 (6)
O2—C3—C2—C1−175.6 (7)C5—C13—C14—C9−179.6 (5)
C4—C3—C2—C1−0.8 (10)C16—C13—C14—C962.9 (6)
C20—N—C15—C16177.7 (6)C20—N—C9—C1062.0 (8)
C9—N—C15—C16−53.7 (7)C15—N—C9—C10−66.7 (7)
N—C15—C16—C1353.3 (6)C20—N—C9—C14−173.6 (5)
C11—C12—C13—C1423.7 (7)C15—N—C9—C1457.7 (6)
C4—C12—C13—C14−165.3 (5)C8—C14—C9—N168.2 (5)
C11—C12—C13—C5141.4 (6)C13—C14—C9—N−63.0 (6)
C4—C12—C13—C5−47.6 (8)C8—C14—C9—C10−61.0 (7)
C11—C12—C13—C16−93.2 (6)C13—C14—C9—C1067.9 (7)
C4—C12—C13—C1677.8 (7)N—C9—C10—C1176.5 (7)
C15—C16—C13—C1262.0 (6)C14—C9—C10—C11−48.2 (7)
C15—C16—C13—C14−57.5 (6)C12—C11—C10—C918.3 (9)
C15—C16—C13—C5−169.8 (5)C1—C11—C10—C9−162.5 (6)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C5—H5A···O10.972.232.853 (9)121
C16—H16B···O10.972.533.102 (10)118
C18—H18B···O20.962.142.812 (16)126
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C5—H5A···O10.972.232.853 (9)121
C16—H16B···O10.972.533.102 (10)118
C18—H18B···O20.962.142.812 (16)126
Acknowledgements top

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

references
References top

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