Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805039231/cv6610sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536805039231/cv6610Isup2.hkl |
CCDC reference: 296546
Codeinone was prepared according to the method of Bakalska et al. (2002). Crystals suitable for X-ray diffraction were obtained by slow evaporation from ethanol at 277 K.
IR spectra were measured on a Bomem–Michelson 100 F T–IR spectrometer in the range 4000–400 cm−1, with 2 cm−1 resolution and 150 scans. Solid-state IR spectra were recorded using the KBr pellet technique. Chloroform (Merck) solutions, at a concentration of 1.10−2 M, were measured using 0.05 cm KBr pellets. The bands at 2840 and 2807 cm−1 of codeinone are assigned to νs[CH3(O)] and νs[CH3(N)] modes, respectively. The most intense peak at 1677 cm−1 in the IR spectrum of codeinone belongs to the ν(C═O) mode of the conjugated C═O group. The maxima at 1374 and 1388 cm−1 indicate δs[CH3(N)] and δs[CH3(O)], respectively. Typical for morphine compounds are peaks at about 1633, 1604 and 1506 cm−1, which are assigned as ν(C ═ C), 8a and 19a in-plane (A1) phenyl modes. The series of in-plane peaks of 1,2,3,4-o-tetrasubstituted benzene at about 1150 and 1050 cm−1 are observed in the 1200–800 cm−1 frequency region. Below 1000 cm−1, an intense maximum at 940 cm−1 and a pair of maxima at about 936 and 804 cm−1 are present, but the exact assignment with conventional IR techniques is ambiguous. A detailed spectroscopic study, combined with ab initio UHF calculations of (I), are in progress and will be published at a later date.
Spectroscopic analysis for codeinone: 1H NMR (Bruker 250, 250 MHz, CDCl3, δ, p.p.m.): 6.67 (d, 1H, J = 8.2 Hz, H-2), 6.62 (d, 1H, J = 10.2 Hz, H-8), 6.59 (d, 1H, J = 8.2 Hz, H-1), 6.07 (dd, 1H, J = 10.2 and 2.9 Hz, H-7), 4.68 (s, 1H, H-5), 3.85 (s, 3H OCH3), 3.45–3.35 (m, 1H, H-9), 3.25–3.17 (m, 1H, H-14), 3.10 (d, 1H, J = 18.5 Hz, H-10β), 2.61 (dm, 1H, J = 11.8 Hz, H-16e), 2.45 (s, 3H, NCH3), 2.30 (dd, 1H, J = 18.5 and 5.5 Hz, H-10α), 2.30 (td, 1H, J = 11.9 and 3.7 Hz, H-16a), 2.06 (td, 1H, J = 12.0 and 4.8 Hz, H-15a), 1.85 (dm, 1H, J = 12.5 Hz, H-15e); 13C NMR (CDCl3, δ, p.p.m.): 119.7 (C-1), 114.7 (C-2), 142.3 (C-3), 146.2 (C-4), 88.0 (C-5), 194.1 (C-6), 132.2 (C-7), 149.1 (C-8), 58.9 (C-9), 20.4 (C-10),126.1 (C-11), 129.0 (C-12), 43.1 (C-13), 41.4 (C-14), 33.9 (C-15), 46.7 (C-16), 42.9 (NMe), 56.7 (OMe).
All H atoms were placed in idealized positions, with C—H = 0.93–0.98 Å, and constrained to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C and Caromatic), or 1.5Ueq(CMe).
Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Version 1.3; Bruno et al., 2002); software used to prepare material for publication: WinGX (Farrugia, 1999).
C18H19NO3 | Dx = 1.346 Mg m−3 |
Mr = 297.34 | Melting point: not measured K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 22 reflections |
a = 7.2541 (10) Å | θ = 16.3–17.7° |
b = 14.0943 (14) Å | µ = 0.09 mm−1 |
c = 14.3507 (15) Å | T = 290 K |
V = 1467.2 (3) Å3 | Prismatic, colourless |
Z = 4 | 0.18 × 0.16 × 0.15 mm |
F(000) = 632 |
Enraf–Nonius CAD-4 diffractometer | Rint = 0.172 |
Radiation source: fine-focus sealed tube | θmax = 28.0°, θmin = 2.0° |
Graphite monochromator | h = 0→9 |
Non–profiled ω/2θ scans | k = −18→18 |
7258 measured reflections | l = −18→18 |
2032 independent reflections | 3 standard reflections every 120 min |
987 reflections with I > 2σ(I) | intensity decay: 2% |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.060 | H-atom parameters constrained |
wR(F2) = 0.118 | w = 1/[σ2(Fo2) + (0.0344P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
2032 reflections | Δρmax = 0.16 e Å−3 |
200 parameters | Δρmin = −0.18 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0128 (18) |
C18H19NO3 | V = 1467.2 (3) Å3 |
Mr = 297.34 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.2541 (10) Å | µ = 0.09 mm−1 |
b = 14.0943 (14) Å | T = 290 K |
c = 14.3507 (15) Å | 0.18 × 0.16 × 0.15 mm |
Enraf–Nonius CAD-4 diffractometer | Rint = 0.172 |
7258 measured reflections | 3 standard reflections every 120 min |
2032 independent reflections | intensity decay: 2% |
987 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.060 | 0 restraints |
wR(F2) = 0.118 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.16 e Å−3 |
2032 reflections | Δρmin = −0.18 e Å−3 |
200 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 1.2910 (6) | 0.4138 (3) | 0.7428 (2) | 0.0481 (10) | |
O1 | 0.5791 (5) | 0.6486 (2) | 0.5119 (2) | 0.0575 (9) | |
O2 | 0.7983 (4) | 0.48246 (17) | 0.49336 (18) | 0.0429 (8) | |
O3 | 0.6008 (6) | 0.3076 (2) | 0.4889 (2) | 0.0700 (11) | |
C1 | 0.7832 (7) | 0.6168 (3) | 0.7470 (3) | 0.0467 (12) | |
H1 | 0.7759 | 0.6433 | 0.8062 | 0.056* | |
C2 | 0.6847 (8) | 0.6569 (3) | 0.6747 (3) | 0.0468 (12) | |
H2 | 0.6181 | 0.7122 | 0.6858 | 0.056* | |
C3 | 0.6818 (7) | 0.6173 (3) | 0.5859 (3) | 0.0409 (11) | |
C4 | 0.7905 (6) | 0.5387 (3) | 0.5723 (3) | 0.0367 (10) | |
C5 | 0.8760 (6) | 0.3921 (3) | 0.5255 (3) | 0.0382 (11) | |
H5 | 0.9501 | 0.3635 | 0.4758 | 0.046* | |
C6 | 0.7138 (7) | 0.3272 (3) | 0.5490 (3) | 0.0474 (12) | |
C7 | 0.6934 (8) | 0.2932 (3) | 0.6438 (3) | 0.0580 (14) | |
H7 | 0.5832 | 0.2643 | 0.6609 | 0.070* | |
C8 | 0.8256 (8) | 0.3018 (3) | 0.7074 (3) | 0.0564 (14) | |
H8 | 0.8029 | 0.2795 | 0.7673 | 0.068* | |
C9 | 1.0988 (7) | 0.3944 (3) | 0.7720 (3) | 0.0436 (12) | |
H9 | 1.1039 | 0.3481 | 0.8228 | 0.052* | |
C10 | 0.9879 (7) | 0.4799 (3) | 0.8073 (3) | 0.0548 (14) | |
H10A | 0.8951 | 0.4574 | 0.8506 | 0.066* | |
H10B | 1.0703 | 0.5214 | 0.8415 | 0.066* | |
C11 | 0.8938 (7) | 0.5371 (3) | 0.7325 (3) | 0.0403 (11) | |
C12 | 0.8970 (7) | 0.5025 (3) | 0.6428 (3) | 0.0374 (11) | |
C13 | 0.9998 (6) | 0.4165 (3) | 0.6086 (3) | 0.0370 (11) | |
C14 | 1.0065 (7) | 0.3447 (3) | 0.6874 (3) | 0.0432 (12) | |
H14 | 1.0889 | 0.2934 | 0.6677 | 0.052* | |
C15 | 1.1965 (7) | 0.4410 (3) | 0.5809 (3) | 0.0467 (12) | |
H15A | 1.2568 | 0.3850 | 0.5562 | 0.056* | |
H15B | 1.1949 | 0.4889 | 0.5324 | 0.056* | |
C16 | 1.3037 (7) | 0.4777 (3) | 0.6639 (3) | 0.0529 (13) | |
H16A | 1.4321 | 0.4854 | 0.6466 | 0.063* | |
H16B | 1.2561 | 0.5394 | 0.6816 | 0.063* | |
C17 | 1.4038 (8) | 0.4485 (4) | 0.8207 (3) | 0.0691 (16) | |
H17A | 1.3950 | 0.4049 | 0.8720 | 0.104* | |
H17B | 1.3601 | 0.5097 | 0.8399 | 0.104* | |
H17C | 1.5300 | 0.4534 | 0.8012 | 0.104* | |
C18 | 0.4366 (8) | 0.7148 (4) | 0.5298 (4) | 0.082 (2) | |
H18A | 0.3755 | 0.7304 | 0.4725 | 0.122* | |
H18B | 0.4884 | 0.7712 | 0.5566 | 0.122* | |
H18C | 0.3494 | 0.6875 | 0.5724 | 0.122* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.041 (2) | 0.058 (2) | 0.045 (2) | 0.001 (2) | −0.006 (2) | 0.0044 (19) |
O1 | 0.063 (2) | 0.0458 (18) | 0.063 (2) | 0.0188 (19) | −0.009 (2) | 0.0017 (17) |
O2 | 0.0564 (19) | 0.0374 (14) | 0.0349 (15) | 0.0056 (16) | −0.0042 (17) | −0.0022 (13) |
O3 | 0.073 (3) | 0.069 (2) | 0.068 (2) | −0.020 (2) | −0.020 (2) | −0.0067 (19) |
C1 | 0.058 (3) | 0.041 (3) | 0.041 (3) | −0.001 (3) | 0.006 (3) | −0.010 (2) |
C2 | 0.054 (3) | 0.033 (2) | 0.053 (3) | 0.001 (3) | 0.003 (3) | −0.005 (2) |
C3 | 0.045 (3) | 0.034 (2) | 0.044 (3) | −0.002 (2) | −0.008 (3) | 0.010 (2) |
C4 | 0.044 (3) | 0.030 (2) | 0.036 (2) | −0.003 (2) | 0.001 (2) | 0.0016 (19) |
C5 | 0.040 (3) | 0.031 (2) | 0.043 (3) | 0.011 (2) | 0.006 (2) | 0.0003 (19) |
C6 | 0.050 (3) | 0.046 (3) | 0.047 (3) | −0.001 (3) | 0.000 (3) | −0.011 (2) |
C7 | 0.058 (4) | 0.052 (3) | 0.064 (3) | −0.023 (3) | 0.007 (3) | 0.002 (3) |
C8 | 0.061 (4) | 0.062 (3) | 0.046 (3) | −0.014 (3) | 0.008 (3) | 0.013 (2) |
C9 | 0.045 (3) | 0.052 (3) | 0.034 (2) | 0.006 (3) | −0.002 (2) | 0.010 (2) |
C10 | 0.057 (3) | 0.068 (3) | 0.040 (3) | 0.001 (3) | −0.005 (3) | −0.003 (2) |
C11 | 0.042 (3) | 0.038 (2) | 0.041 (3) | −0.005 (2) | −0.001 (2) | −0.002 (2) |
C12 | 0.039 (3) | 0.034 (2) | 0.038 (3) | −0.008 (2) | 0.000 (2) | 0.003 (2) |
C13 | 0.034 (3) | 0.039 (2) | 0.039 (3) | −0.003 (2) | 0.004 (2) | 0.002 (2) |
C14 | 0.047 (3) | 0.042 (2) | 0.041 (2) | 0.001 (3) | 0.001 (2) | 0.006 (2) |
C15 | 0.044 (3) | 0.051 (3) | 0.045 (3) | 0.004 (3) | 0.006 (3) | 0.003 (2) |
C16 | 0.036 (3) | 0.059 (3) | 0.064 (3) | −0.005 (3) | 0.003 (3) | 0.003 (3) |
C17 | 0.049 (3) | 0.089 (4) | 0.070 (4) | 0.003 (3) | −0.018 (3) | −0.008 (3) |
C18 | 0.093 (5) | 0.068 (4) | 0.084 (4) | 0.034 (4) | −0.028 (4) | −0.003 (3) |
N1—C16 | 1.450 (5) | C9—C10 | 1.535 (6) |
N1—C17 | 1.469 (6) | C9—C14 | 1.553 (6) |
N1—C9 | 1.482 (6) | C9—H9 | 0.9800 |
O1—C3 | 1.371 (5) | C10—C11 | 1.506 (6) |
O1—C18 | 1.415 (6) | C10—H10A | 0.9700 |
O2—C4 | 1.384 (4) | C10—H10B | 0.9700 |
O2—C5 | 1.468 (4) | C11—C12 | 1.377 (5) |
O3—C6 | 1.221 (5) | C12—C13 | 1.505 (6) |
C1—C2 | 1.380 (6) | C13—C14 | 1.519 (5) |
C1—C11 | 1.396 (6) | C13—C15 | 1.521 (6) |
C1—H1 | 0.9300 | C14—H14 | 0.9800 |
C2—C3 | 1.391 (5) | C15—C16 | 1.513 (6) |
C2—H2 | 0.9300 | C15—H15A | 0.9700 |
C3—C4 | 1.374 (5) | C15—H15B | 0.9700 |
C4—C12 | 1.370 (5) | C16—H16A | 0.9700 |
C5—C6 | 1.527 (6) | C16—H16B | 0.9700 |
C5—C13 | 1.532 (6) | C17—H17A | 0.9600 |
C5—H5 | 0.9800 | C17—H17B | 0.9600 |
C6—C7 | 1.450 (6) | C17—H17C | 0.9600 |
C7—C8 | 1.329 (7) | C18—H18A | 0.9600 |
C7—H7 | 0.9300 | C18—H18B | 0.9600 |
C8—C14 | 1.473 (6) | C18—H18C | 0.9600 |
C8—H8 | 0.9300 | ||
C16—N1—C17 | 110.6 (4) | H10A—C10—H10B | 107.5 |
C16—N1—C9 | 113.3 (4) | C12—C11—C1 | 115.7 (4) |
C17—N1—C9 | 111.7 (4) | C12—C11—C10 | 118.0 (4) |
C3—O1—C18 | 117.9 (4) | C1—C11—C10 | 125.8 (4) |
C4—O2—C5 | 104.8 (3) | C4—C12—C11 | 123.3 (4) |
C2—C1—C11 | 121.0 (4) | C4—C12—C13 | 109.8 (4) |
C2—C1—H1 | 119.5 | C11—C12—C13 | 126.7 (4) |
C11—C1—H1 | 119.5 | C12—C13—C14 | 108.0 (3) |
C1—C2—C3 | 122.1 (4) | C12—C13—C15 | 111.6 (4) |
C1—C2—H2 | 118.9 | C14—C13—C15 | 108.4 (4) |
C3—C2—H2 | 118.9 | C12—C13—C5 | 98.3 (4) |
O1—C3—C4 | 117.5 (4) | C14—C13—C5 | 116.6 (4) |
O1—C3—C2 | 126.1 (4) | C15—C13—C5 | 113.4 (4) |
C4—C3—C2 | 116.4 (4) | C8—C14—C13 | 113.0 (4) |
C12—C4—C3 | 121.2 (4) | C8—C14—C9 | 114.7 (4) |
C12—C4—O2 | 111.6 (3) | C13—C14—C9 | 107.2 (4) |
C3—C4—O2 | 127.0 (4) | C8—C14—H14 | 107.2 |
O2—C5—C6 | 107.0 (3) | C13—C14—H14 | 107.2 |
O2—C5—C13 | 105.9 (3) | C9—C14—H14 | 107.2 |
C6—C5—C13 | 114.5 (3) | C16—C15—C13 | 110.7 (4) |
O2—C5—H5 | 109.8 | C16—C15—H15A | 109.5 |
C6—C5—H5 | 109.8 | C13—C15—H15A | 109.5 |
C13—C5—H5 | 109.8 | C16—C15—H15B | 109.5 |
O3—C6—C7 | 121.3 (5) | C13—C15—H15B | 109.5 |
O3—C6—C5 | 119.7 (4) | H15A—C15—H15B | 108.1 |
C7—C6—C5 | 118.9 (4) | N1—C16—C15 | 111.7 (4) |
C8—C7—C6 | 122.7 (5) | N1—C16—H16A | 109.3 |
C8—C7—H7 | 118.6 | C15—C16—H16A | 109.3 |
C6—C7—H7 | 118.6 | N1—C16—H16B | 109.3 |
C7—C8—C14 | 123.1 (4) | C15—C16—H16B | 109.3 |
C7—C8—H8 | 118.4 | H16A—C16—H16B | 107.9 |
C14—C8—H8 | 118.4 | N1—C17—H17A | 109.5 |
N1—C9—C10 | 116.2 (4) | N1—C17—H17B | 109.5 |
N1—C9—C14 | 105.5 (4) | H17A—C17—H17B | 109.5 |
C10—C9—C14 | 112.7 (4) | N1—C17—H17C | 109.5 |
N1—C9—H9 | 107.3 | H17A—C17—H17C | 109.5 |
C10—C9—H9 | 107.3 | H17B—C17—H17C | 109.5 |
C14—C9—H9 | 107.3 | O1—C18—H18A | 109.5 |
C11—C10—C9 | 115.0 (4) | O1—C18—H18B | 109.5 |
C11—C10—H10A | 108.5 | H18A—C18—H18B | 109.5 |
C9—C10—H10A | 108.5 | O1—C18—H18C | 109.5 |
C11—C10—H10B | 108.5 | H18A—C18—H18C | 109.5 |
C9—C10—H10B | 108.5 | H18B—C18—H18C | 109.5 |
C18—O1—C3—C2 | −13.1 (7) | C6—C5—C13—C15 | 154.1 (4) |
C18—O1—C3—C4 | 165.8 (4) | O3—C6—C7—C8 | 170.2 (5) |
C5—O2—C4—C3 | −159.3 (4) | C5—C6—C7—C8 | −12.2 (7) |
C5—O2—C4—C12 | 15.8 (4) | C6—C7—C8—C14 | −1.2 (8) |
C4—O2—C5—C6 | 93.4 (4) | C7—C8—C14—C9 | 150.2 (5) |
C4—O2—C5—C13 | −29.1 (4) | C7—C8—C14—C13 | 26.9 (7) |
C16—N1—C9—C10 | −63.2 (5) | N1—C9—C10—C11 | 85.8 (5) |
C16—N1—C9—C14 | 62.5 (5) | C14—C9—C10—C11 | −36.2 (6) |
C17—N1—C9—C10 | 62.6 (5) | N1—C9—C14—C8 | 168.3 (4) |
C17—N1—C9—C14 | −171.8 (4) | N1—C9—C14—C13 | −65.4 (5) |
C9—N1—C16—C15 | −56.6 (5) | C10—C9—C14—C8 | −63.9 (5) |
C17—N1—C16—C15 | 177.1 (4) | C10—C9—C14—C13 | 62.4 (5) |
C11—C1—C2—C3 | 3.8 (7) | C9—C10—C11—C1 | 179.0 (4) |
C2—C1—C11—C10 | −171.8 (5) | C9—C10—C11—C12 | 7.3 (6) |
C2—C1—C11—C12 | 0.1 (7) | C1—C11—C12—C4 | −4.2 (6) |
C1—C2—C3—O1 | 175.6 (5) | C1—C11—C12—C13 | −178.3 (4) |
C1—C2—C3—C4 | −3.4 (7) | C10—C11—C12—C4 | 168.3 (4) |
O1—C3—C4—O2 | −5.1 (6) | C10—C11—C12—C13 | −5.8 (7) |
O1—C3—C4—C12 | −179.8 (4) | C4—C12—C13—C5 | −21.0 (4) |
C2—C3—C4—O2 | 173.9 (4) | C4—C12—C13—C14 | −142.6 (4) |
C2—C3—C4—C12 | −0.7 (6) | C4—C12—C13—C15 | 98.4 (4) |
O2—C4—C12—C11 | −170.7 (4) | C11—C12—C13—C5 | 153.7 (4) |
O2—C4—C12—C13 | 4.2 (5) | C11—C12—C13—C14 | 32.1 (6) |
C3—C4—C12—C11 | 4.7 (6) | C11—C12—C13—C15 | −86.9 (5) |
C3—C4—C12—C13 | 179.6 (4) | C5—C13—C14—C8 | −39.1 (6) |
O2—C5—C6—O3 | 58.9 (5) | C5—C13—C14—C9 | −166.4 (4) |
O2—C5—C6—C7 | −118.7 (4) | C12—C13—C14—C8 | 70.3 (5) |
C13—C5—C6—O3 | 176.0 (4) | C12—C13—C14—C9 | −56.9 (5) |
C13—C5—C6—C7 | −1.6 (5) | C15—C13—C14—C8 | −168.6 (4) |
O2—C5—C13—C12 | 29.7 (4) | C15—C13—C14—C9 | 64.1 (5) |
O2—C5—C13—C14 | 144.8 (4) | C5—C13—C15—C16 | 172.0 (3) |
O2—C5—C13—C15 | −88.2 (4) | C12—C13—C15—C16 | 62.1 (4) |
C6—C5—C13—C12 | −87.9 (4) | C14—C13—C15—C16 | −56.7 (5) |
C6—C5—C13—C14 | 27.1 (5) | C13—C15—C16—N1 | 52.0 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
C18—H18A···O1i | 0.96 | 2.75 | 3.285 (6) | 116 |
C10—H10A···O2ii | 0.97 | 2.62 | 3.423 (5) | 140 |
C14—H14···O3iii | 0.98 | 2.66 | 3.389 (6) | 131 |
C5—H5···O3iii | 0.98 | 2.70 | 3.260 (5) | 117 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1/2, −y+1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C18H19NO3 |
Mr | 297.34 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 290 |
a, b, c (Å) | 7.2541 (10), 14.0943 (14), 14.3507 (15) |
V (Å3) | 1467.2 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.18 × 0.16 × 0.15 |
Data collection | |
Diffractometer | Enraf–Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7258, 2032, 987 |
Rint | 0.172 |
(sin θ/λ)max (Å−1) | 0.660 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.060, 0.118, 1.02 |
No. of reflections | 2032 |
No. of parameters | 200 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.16, −0.18 |
Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), CAD-4 EXPRESS, XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Version 1.3; Bruno et al., 2002), WinGX (Farrugia, 1999).
C16—N1—C9—C14 | 62.5 (5) | C14—C9—C10—C11 | −36.2 (6) |
O2—C4—C12—C13 | 4.2 (5) | C10—C11—C12—C13 | −5.8 (7) |
C13—C5—C6—C7 | −1.6 (5) | C4—C12—C13—C5 | −21.0 (4) |
O2—C5—C13—C14 | 144.8 (4) | C11—C12—C13—C15 | −86.9 (5) |
C6—C7—C8—C14 | −1.2 (8) | C15—C13—C14—C9 | 64.1 (5) |
C7—C8—C14—C13 | 26.9 (7) | C13—C15—C16—N1 | 52.0 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
C18—H18A···O1i | 0.96 | 2.75 | 3.285 (6) | 116 |
C10—H10A···O2ii | 0.97 | 2.62 | 3.423 (5) | 140 |
C14—H14···O3iii | 0.98 | 2.66 | 3.389 (6) | 131 |
C5—H5···O3iii | 0.98 | 2.70 | 3.260 (5) | 117 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1/2, −y+1/2, −z+1. |
The structure of codeinone, (I), was elucidated as part of our synthetic, spectroscopic and structural investigations of morphine alkaloids, which constitute a major class of pain-alleviating drugs. Codeinone has been found to possess antitumour potential, with high cytotoxic activity against human promyelocytic leukaemic cell lines (Hitosugi et al., 2003). The transformation of morphine derivatives into different metabolites is a matter of practical interest for detecting opiates in blood or urine. It is known that codeinone in the living cell is produced from the reaction of codeine with nicotinamide adenine dinucleotide phosphate (NADP+).
The overall configuration of (I) and the atom-numbering scheme are shown in Fig. 1. The absolute configuration of the chiral centres in the molecule is identical to that of the starting material, codeine. The main structural features of the molecule are very close to those of codeine (Canfield et al., 1987), heroin (Canfield et al., 1979), morphine (Gylbert, 1973) and acetylcodeine (Sonar et al., 2005; Kolev et al., 2005).
The molecule of (I) exhibits the T-shaped configuration characteristic of classical morphine opiates. The value of 86.62 (6)° for the dihedral angle between the mean planes of the A/B/C and D/E rings in (I) is comparable with that in codeine (88.94°; Canfield et al., 1987) and differs somewhat with that observed in 6-O-codeine [80.56 (8)°; Sonar et al., 2005; Kolev et al., 2005].
The ring fusions and conformations are similar to those previously reported for morphine derivatives (Gelders & de Ranter, 1979; Petrickova et al., 2002; Moody et al., 1997). Aromatic ring A is planar, B is close to an envelope, C and D assume half-chair conformations and E assumes a chair form (Table 1). The oxidation of codeine to codeinone should mainly affect the shape and properties of ring D. However, no major differences between the geometric parameters of ring D in codeinone, codeine and even 6-O-codeine could be established.
The conformation about the single C—C bonds within the rings is staggered, as in codeine; exceptions such as the C5—C6 eclipsed bond in 6-O-codeine are not present. This difference between the codeinone and 6-acetylcodeine conformations, along with the absence or presence of a chiral centre at the C6 position, is associated with the different functional groups attached to atom C6.
In the three-dimensional arrangement of the molecules of (I) (Fig. 2), no classical hydrogen bonds could be found. A subsequent examination of intermolecular contacts suggested that molecules of (I) are linked in the crystal structure through weak C—H···O interactions (Desiraju, 1996; Steiner & Desiraju, 1998; Zhu et al., 2005). The interactions involving atoms O1 and O3 (Table 2) connect the molecules to form undulating `pseudo'-layers perpendicular to the c axis. The C10—H10A···O2 interaction connects the layers along the c axis, spreading the structure stabilization in all three directions.