Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270112040188/uk3053sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270112040188/uk3053Isup2.hkl |
CCDC reference: 914649
To a stirred solution of oxycodone (0.315 g, 1 mmol) in chloroform (30 ml) maintained at 273–278 K, was added 3-chloroperbenzoic acid (0.259 g, 1.5 mmol) in small portions. After complete addition of 3-chloroperbenzoic acid, stirring was continued at room temperature for 12 h. The solution was passed through basic alumina (110–200 mesh) and traces of unreacted oxycodone were removed by washing with chloroform. Elution with methanol–chloroform (1:3 v/v) afforded oxycodone N-oxide. The crude product was crystallized from chloroform as colourless crystals, which were suitable for X-ray analysis. Spectroscopic analysis: 1H NMR (CDCl3, δ, p.p.m.): 1.56–1.74 (m, 2H), 1.94–2.01 (m, 1H), 2.20–2.27 (m, 1H), 3.08–3.30 (m, 6H), 3.31 (s, 3H), 3.60 (d, 1H), 3.90 (s, 3H), 4.77 (s, 1H), 6.65 (d, 1H), 6.75 (d, 1H), 12.34 (s, 1H); 13C NMR (CDCl3, δ, p.p.m.): 26.1, 29.0, 33.2, 35.2, 50.2, 57.1, 59.8, 62.0, 72.5, 76.0, 90.1, 116.0, 120.2, 120.4, 129.4, 144.1, 145.5, 207.8.
H atoms were found in difference Fourier maps and subsequently placed in idealized positions, with constrained distances of 0.95 (CAr—H), 0.98 (RCH3), 0.99 (R2CH2), 1.00 (R3CH) and 0.84 Å (OH). Uiso(H) values were set to 1.2Ueq(CArH, R2CH2, R3CH) or 1.5Ueq(RCH3, OH) of the parent atom.
Since there was no measurable anomalous signal, Friedel pairs were merged. The absolute structure of the compound was determined from the synthesis.
Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX97-2 (Sheldrick, 2008) and local procedures.
C18H21NO5 | F(000) = 704 |
Mr = 331.36 | Dx = 1.462 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 2010 reflections |
a = 7.2080 (1) Å | θ = 1.0–27.5° |
b = 12.7611 (3) Å | µ = 0.11 mm−1 |
c = 16.3676 (4) Å | T = 90 K |
V = 1505.52 (6) Å3 | Irregular block, colourless |
Z = 4 | 0.22 × 0.20 × 0.15 mm |
Nonius KappaCCD area-detector diffractometer | 1988 independent reflections |
Radiation source: fine-focus sealed tube | 1746 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.023 |
Detector resolution: 18 pixels mm-1 | θmax = 27.5°, θmin = 2.0° |
ω scans at fixed χ = 55° | h = −9→9 |
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | k = −16→16 |
Tmin = 0.977, Tmax = 0.984 | l = −21→21 |
3445 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.034 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.081 | H-atom parameters constrained |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0417P)2 + 0.3029P] where P = (Fo2 + 2Fc2)/3 |
1988 reflections | (Δ/σ)max < 0.001 |
220 parameters | Δρmax = 0.24 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
C18H21NO5 | V = 1505.52 (6) Å3 |
Mr = 331.36 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.2080 (1) Å | µ = 0.11 mm−1 |
b = 12.7611 (3) Å | T = 90 K |
c = 16.3676 (4) Å | 0.22 × 0.20 × 0.15 mm |
Nonius KappaCCD area-detector diffractometer | 1988 independent reflections |
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | 1746 reflections with I > 2σ(I) |
Tmin = 0.977, Tmax = 0.984 | Rint = 0.023 |
3445 measured reflections |
R[F2 > 2σ(F2)] = 0.034 | 0 restraints |
wR(F2) = 0.081 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.24 e Å−3 |
1988 reflections | Δρmin = −0.21 e Å−3 |
220 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. In the absence of any significant anomalous scattering, Friedel pairs were merged for the final cycles of least-squares refinement. 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 > 2σ(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 | ||
C1 | 0.3016 (3) | 1.20159 (15) | 0.06279 (11) | 0.0147 (4) | |
H1 | 0.1848 | 1.2343 | 0.0543 | 0.018* | |
C2 | 0.4411 (3) | 1.25459 (15) | 0.10378 (11) | 0.0154 (4) | |
H2 | 0.4166 | 1.3236 | 0.1228 | 0.019* | |
C3 | 0.6170 (3) | 1.21116 (15) | 0.11858 (11) | 0.0133 (4) | |
C4 | 0.6434 (3) | 1.10873 (15) | 0.09187 (12) | 0.0132 (4) | |
C5 | 0.7225 (3) | 0.93839 (15) | 0.09201 (12) | 0.0143 (4) | |
H5 | 0.8221 | 0.8893 | 0.0735 | 0.017* | |
C6 | 0.6397 (3) | 0.90168 (15) | 0.17395 (12) | 0.0160 (4) | |
C7 | 0.4885 (3) | 0.82149 (15) | 0.16823 (12) | 0.0160 (4) | |
H7A | 0.4386 | 0.8069 | 0.2234 | 0.019* | |
H7B | 0.5395 | 0.7554 | 0.1460 | 0.019* | |
C8 | 0.3317 (3) | 0.86096 (16) | 0.11264 (11) | 0.0141 (4) | |
H8A | 0.2279 | 0.8101 | 0.1126 | 0.017* | |
H8B | 0.2844 | 0.9290 | 0.1330 | 0.017* | |
C9 | 0.2608 (3) | 0.92092 (15) | −0.03283 (11) | 0.0132 (4) | |
H9 | 0.1523 | 0.8721 | −0.0332 | 0.016* | |
C10 | 0.1887 (3) | 1.02933 (14) | −0.00568 (12) | 0.0143 (4) | |
H10A | 0.1375 | 1.0659 | −0.0540 | 0.017* | |
H10B | 0.0857 | 1.0189 | 0.0335 | 0.017* | |
C11 | 0.3327 (3) | 1.09923 (14) | 0.03368 (11) | 0.0127 (4) | |
C12 | 0.5060 (3) | 1.05840 (15) | 0.04889 (11) | 0.0122 (4) | |
C13 | 0.5729 (3) | 0.95099 (15) | 0.02522 (11) | 0.0122 (4) | |
C14 | 0.4083 (3) | 0.87383 (15) | 0.02601 (12) | 0.0129 (4) | |
C15 | 0.6570 (3) | 0.95335 (16) | −0.06137 (11) | 0.0148 (4) | |
H15A | 0.7644 | 1.0017 | −0.0622 | 0.018* | |
H15B | 0.7021 | 0.8825 | −0.0759 | 0.018* | |
C16 | 0.5150 (3) | 0.98887 (15) | −0.12392 (12) | 0.0157 (4) | |
H16A | 0.4822 | 1.0630 | −0.1136 | 0.019* | |
H16B | 0.5695 | 0.9841 | −0.1793 | 0.019* | |
N17 | 0.3418 (2) | 0.92248 (13) | −0.12008 (10) | 0.0144 (4) | |
C18 | 0.2051 (3) | 0.96126 (16) | −0.18133 (12) | 0.0191 (5) | |
H18A | 0.2487 | 0.9442 | −0.2365 | 0.029* | |
H18B | 0.1920 | 1.0374 | −0.1760 | 0.029* | |
H18C | 0.0847 | 0.9277 | −0.1718 | 0.029* | |
O19 | 0.7461 (2) | 1.27432 (10) | 0.15561 (8) | 0.0158 (3) | |
C20 | 0.8802 (3) | 1.22387 (16) | 0.20839 (12) | 0.0184 (4) | |
H20A | 0.8156 | 1.1774 | 0.2466 | 0.028* | |
H20B | 0.9487 | 1.2772 | 0.2391 | 0.028* | |
H20C | 0.9670 | 1.1828 | 0.1752 | 0.028* | |
O21 | 0.7970 (2) | 1.04401 (10) | 0.10352 (8) | 0.0153 (3) | |
O22 | 0.6926 (2) | 0.93888 (12) | 0.23779 (9) | 0.0264 (4) | |
O23 | 0.4629 (2) | 0.77234 (9) | 0.00009 (9) | 0.0149 (3) | |
H23 | 0.4567 | 0.7687 | −0.0511 | 0.022* | |
O24 | 0.3857 (2) | 0.81906 (10) | −0.14319 (8) | 0.0169 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0159 (10) | 0.0141 (9) | 0.0142 (9) | 0.0024 (8) | 0.0026 (9) | 0.0027 (8) |
C2 | 0.0217 (11) | 0.0115 (9) | 0.0132 (9) | 0.0006 (9) | 0.0029 (9) | −0.0005 (8) |
C3 | 0.0167 (10) | 0.0124 (9) | 0.0109 (8) | −0.0022 (8) | 0.0020 (9) | −0.0005 (7) |
C4 | 0.0117 (9) | 0.0128 (9) | 0.0152 (9) | −0.0006 (8) | 0.0032 (9) | 0.0015 (8) |
C5 | 0.0133 (10) | 0.0096 (9) | 0.0199 (9) | −0.0005 (8) | 0.0007 (9) | −0.0016 (8) |
C6 | 0.0143 (10) | 0.0147 (9) | 0.0189 (10) | 0.0026 (9) | −0.0018 (9) | 0.0011 (8) |
C7 | 0.0188 (11) | 0.0123 (9) | 0.0171 (9) | −0.0030 (9) | −0.0007 (9) | 0.0025 (8) |
C8 | 0.0127 (10) | 0.0140 (9) | 0.0156 (9) | −0.0020 (9) | 0.0013 (8) | 0.0008 (8) |
C9 | 0.0139 (10) | 0.0116 (9) | 0.0140 (9) | −0.0021 (8) | 0.0034 (8) | 0.0000 (8) |
C10 | 0.0130 (10) | 0.0132 (9) | 0.0168 (9) | 0.0008 (9) | −0.0003 (9) | 0.0000 (8) |
C11 | 0.0144 (10) | 0.0115 (9) | 0.0122 (8) | −0.0011 (8) | 0.0018 (8) | 0.0009 (7) |
C12 | 0.0136 (10) | 0.0098 (9) | 0.0130 (8) | −0.0012 (8) | 0.0040 (9) | 0.0005 (8) |
C13 | 0.0104 (10) | 0.0102 (9) | 0.0158 (9) | 0.0000 (8) | 0.0010 (8) | 0.0008 (8) |
C14 | 0.0131 (10) | 0.0104 (9) | 0.0151 (9) | 0.0004 (8) | 0.0012 (8) | −0.0011 (7) |
C15 | 0.0128 (10) | 0.0129 (9) | 0.0186 (9) | −0.0023 (9) | 0.0050 (9) | −0.0019 (8) |
C16 | 0.0165 (11) | 0.0128 (9) | 0.0177 (9) | −0.0022 (9) | 0.0048 (9) | −0.0001 (8) |
N17 | 0.0171 (9) | 0.0114 (7) | 0.0147 (8) | −0.0001 (7) | 0.0020 (7) | −0.0016 (6) |
C18 | 0.0240 (12) | 0.0170 (10) | 0.0161 (9) | −0.0008 (10) | −0.0037 (9) | 0.0003 (8) |
O19 | 0.0185 (7) | 0.0118 (6) | 0.0170 (6) | −0.0012 (6) | −0.0043 (6) | 0.0002 (6) |
C20 | 0.0185 (11) | 0.0185 (10) | 0.0182 (9) | −0.0005 (9) | −0.0040 (9) | −0.0011 (8) |
O21 | 0.0122 (7) | 0.0103 (6) | 0.0234 (7) | 0.0001 (6) | 0.0001 (6) | −0.0016 (6) |
O22 | 0.0305 (9) | 0.0282 (8) | 0.0206 (7) | −0.0091 (8) | −0.0067 (7) | 0.0017 (7) |
O23 | 0.0176 (7) | 0.0094 (7) | 0.0177 (6) | −0.0001 (6) | 0.0006 (6) | −0.0018 (6) |
O24 | 0.0226 (8) | 0.0094 (6) | 0.0188 (7) | 0.0022 (6) | 0.0019 (7) | −0.0041 (6) |
C1—C2 | 1.385 (3) | C10—C11 | 1.512 (3) |
C1—C11 | 1.408 (3) | C10—H10A | 0.9900 |
C1—H1 | 0.9500 | C10—H10B | 0.9900 |
C2—C3 | 1.405 (3) | C11—C12 | 1.376 (3) |
C2—H2 | 0.9500 | C12—C13 | 1.504 (3) |
C3—O19 | 1.372 (2) | C13—C15 | 1.542 (3) |
C3—C4 | 1.391 (3) | C13—C14 | 1.542 (3) |
C4—C12 | 1.374 (3) | C14—O23 | 1.419 (2) |
C4—O21 | 1.394 (2) | C15—C16 | 1.517 (3) |
C5—O21 | 1.463 (2) | C15—H15A | 0.9900 |
C5—C6 | 1.541 (3) | C15—H15B | 0.9900 |
C5—C13 | 1.544 (3) | C16—N17 | 1.510 (3) |
C5—H5 | 1.0000 | C16—H16A | 0.9900 |
C6—O22 | 1.209 (2) | C16—H16B | 0.9900 |
C6—C7 | 1.498 (3) | N17—O24 | 1.409 (2) |
C7—C8 | 1.536 (3) | N17—C18 | 1.490 (3) |
C7—H7A | 0.9900 | C18—H18A | 0.9800 |
C7—H7B | 0.9900 | C18—H18B | 0.9800 |
C8—C14 | 1.530 (3) | C18—H18C | 0.9800 |
C8—H8A | 0.9900 | O19—C20 | 1.447 (2) |
C8—H8B | 0.9900 | C20—H20A | 0.9800 |
C9—N17 | 1.543 (2) | C20—H20B | 0.9800 |
C9—C10 | 1.543 (3) | C20—H20C | 0.9800 |
C9—C14 | 1.555 (3) | O23—H23 | 0.8400 |
C9—H9 | 1.0000 | ||
C2—C1—C11 | 120.09 (19) | C4—C12—C11 | 124.74 (18) |
C2—C1—H1 | 120.0 | C4—C12—C13 | 109.08 (17) |
C11—C1—H1 | 120.0 | C11—C12—C13 | 126.12 (18) |
C1—C2—C3 | 123.10 (18) | C12—C13—C15 | 110.19 (16) |
C1—C2—H2 | 118.5 | C12—C13—C14 | 109.46 (16) |
C3—C2—H2 | 118.5 | C15—C13—C14 | 108.84 (15) |
O19—C3—C4 | 126.72 (19) | C12—C13—C5 | 97.84 (15) |
O19—C3—C2 | 117.16 (16) | C15—C13—C5 | 112.22 (16) |
C4—C3—C2 | 116.10 (18) | C14—C13—C5 | 117.71 (15) |
C12—C4—C3 | 120.08 (19) | O23—C14—C8 | 106.21 (15) |
C12—C4—O21 | 111.44 (16) | O23—C14—C13 | 111.53 (16) |
C3—C4—O21 | 128.47 (18) | C8—C14—C13 | 110.73 (15) |
O21—C5—C6 | 108.07 (15) | O23—C14—C9 | 110.93 (15) |
O21—C5—C13 | 104.58 (14) | C8—C14—C9 | 111.64 (16) |
C6—C5—C13 | 112.17 (17) | C13—C14—C9 | 105.90 (15) |
O21—C5—H5 | 110.6 | C16—C15—C13 | 111.16 (16) |
C6—C5—H5 | 110.6 | C16—C15—H15A | 109.4 |
C13—C5—H5 | 110.6 | C13—C15—H15A | 109.4 |
O22—C6—C7 | 123.48 (19) | C16—C15—H15B | 109.4 |
O22—C6—C5 | 120.70 (18) | C13—C15—H15B | 109.4 |
C7—C6—C5 | 115.79 (16) | H15A—C15—H15B | 108.0 |
C6—C7—C8 | 110.39 (15) | N17—C16—C15 | 111.23 (15) |
C6—C7—H7A | 109.6 | N17—C16—H16A | 109.4 |
C8—C7—H7A | 109.6 | C15—C16—H16A | 109.4 |
C6—C7—H7B | 109.6 | N17—C16—H16B | 109.4 |
C8—C7—H7B | 109.6 | C15—C16—H16B | 109.4 |
H7A—C7—H7B | 108.1 | H16A—C16—H16B | 108.0 |
C14—C8—C7 | 108.57 (16) | O24—N17—C18 | 106.20 (15) |
C14—C8—H8A | 110.0 | O24—N17—C16 | 109.18 (15) |
C7—C8—H8A | 110.0 | C18—N17—C16 | 109.40 (14) |
C14—C8—H8B | 110.0 | O24—N17—C9 | 108.75 (14) |
C7—C8—H8B | 110.0 | C18—N17—C9 | 112.15 (16) |
H8A—C8—H8B | 108.4 | C16—N17—C9 | 111.00 (14) |
N17—C9—C10 | 112.48 (15) | N17—C18—H18A | 109.5 |
N17—C9—C14 | 108.64 (15) | N17—C18—H18B | 109.5 |
C10—C9—C14 | 113.47 (16) | H18A—C18—H18B | 109.5 |
N17—C9—H9 | 107.3 | N17—C18—H18C | 109.5 |
C10—C9—H9 | 107.3 | H18A—C18—H18C | 109.5 |
C14—C9—H9 | 107.3 | H18B—C18—H18C | 109.5 |
C11—C10—C9 | 114.86 (17) | C3—O19—C20 | 117.07 (15) |
C11—C10—H10A | 108.6 | O19—C20—H20A | 109.5 |
C9—C10—H10A | 108.6 | O19—C20—H20B | 109.5 |
C11—C10—H10B | 108.6 | H20A—C20—H20B | 109.5 |
C9—C10—H10B | 108.6 | O19—C20—H20C | 109.5 |
H10A—C10—H10B | 107.5 | H20A—C20—H20C | 109.5 |
C12—C11—C1 | 115.75 (18) | H20B—C20—H20C | 109.5 |
C12—C11—C10 | 118.46 (17) | C4—O21—C5 | 103.67 (14) |
C1—C11—C10 | 125.59 (19) | C14—O23—H23 | 109.5 |
C11—C1—C2—C3 | 0.0 (3) | C6—C5—C13—C14 | −34.6 (2) |
C1—C2—C3—O19 | 176.25 (17) | C7—C8—C14—O23 | 62.85 (19) |
C1—C2—C3—C4 | −2.1 (3) | C7—C8—C14—C13 | −58.4 (2) |
O19—C3—C4—C12 | −173.94 (18) | C7—C8—C14—C9 | −176.12 (15) |
C2—C3—C4—C12 | 4.2 (3) | C12—C13—C14—O23 | 177.08 (15) |
O19—C3—C4—O21 | 7.0 (3) | C15—C13—C14—O23 | 56.6 (2) |
C2—C3—C4—O21 | −174.82 (17) | C5—C13—C14—O23 | −72.5 (2) |
O21—C5—C6—O22 | −24.0 (3) | C12—C13—C14—C8 | −64.9 (2) |
C13—C5—C6—O22 | −138.7 (2) | C15—C13—C14—C8 | 174.65 (16) |
O21—C5—C6—C7 | 154.04 (16) | C5—C13—C14—C8 | 45.6 (2) |
C13—C5—C6—C7 | 39.3 (2) | C12—C13—C14—C9 | 56.31 (19) |
O22—C6—C7—C8 | 122.7 (2) | C15—C13—C14—C9 | −64.18 (19) |
C5—C6—C7—C8 | −55.2 (2) | C5—C13—C14—C9 | 166.73 (16) |
C6—C7—C8—C14 | 64.1 (2) | N17—C9—C14—O23 | −56.82 (19) |
N17—C9—C10—C11 | −87.7 (2) | C10—C9—C14—O23 | 177.27 (16) |
C14—C9—C10—C11 | 36.1 (2) | N17—C9—C14—C8 | −175.07 (15) |
C2—C1—C11—C12 | 0.0 (3) | C10—C9—C14—C8 | 59.0 (2) |
C2—C1—C11—C10 | 174.67 (18) | N17—C9—C14—C13 | 64.34 (18) |
C9—C10—C11—C12 | −6.0 (2) | C10—C9—C14—C13 | −61.6 (2) |
C9—C10—C11—C1 | 179.44 (17) | C12—C13—C15—C16 | −59.9 (2) |
C3—C4—C12—C11 | −4.6 (3) | C14—C13—C15—C16 | 60.2 (2) |
O21—C4—C12—C11 | 174.58 (16) | C5—C13—C15—C16 | −167.76 (15) |
C3—C4—C12—C13 | 178.05 (17) | C13—C15—C16—N17 | −54.5 (2) |
O21—C4—C12—C13 | −2.8 (2) | C15—C16—N17—O24 | −65.20 (19) |
C1—C11—C12—C4 | 2.3 (3) | C15—C16—N17—C18 | 178.96 (16) |
C10—C11—C12—C4 | −172.74 (18) | C15—C16—N17—C9 | 54.7 (2) |
C1—C11—C12—C13 | 179.22 (17) | C10—C9—N17—O24 | −173.78 (16) |
C10—C11—C12—C13 | 4.2 (3) | C14—C9—N17—O24 | 59.75 (18) |
C4—C12—C13—C15 | −94.21 (19) | C10—C9—N17—C18 | −56.6 (2) |
C11—C12—C13—C15 | 88.5 (2) | C14—C9—N17—C18 | 176.89 (15) |
C4—C12—C13—C14 | 146.13 (16) | C10—C9—N17—C16 | 66.1 (2) |
C11—C12—C13—C14 | −31.2 (3) | C14—C9—N17—C16 | −60.39 (18) |
C4—C12—C13—C5 | 23.01 (19) | C4—C3—O19—C20 | −33.7 (3) |
C11—C12—C13—C5 | −154.31 (18) | C2—C3—O19—C20 | 148.20 (17) |
O21—C5—C13—C12 | −34.57 (17) | C12—C4—O21—C5 | −20.43 (19) |
C6—C5—C13—C12 | 82.31 (18) | C3—C4—O21—C5 | 158.66 (19) |
O21—C5—C13—C15 | 81.06 (18) | C6—C5—O21—C4 | −84.92 (17) |
C6—C5—C13—C15 | −162.06 (16) | C13—C5—O21—C4 | 34.76 (18) |
O21—C5—C13—C14 | −151.46 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
O23—H23···O24 | 0.84 | 1.72 | 2.483 (2) | 151 |
C5—H5···O23i | 1.00 | 2.60 | 3.536 (2) | 157 |
C9—H9···O23ii | 1.00 | 2.36 | 3.314 (2) | 160 |
C16—H16B···O22iii | 0.99 | 2.40 | 3.227 (3) | 141 |
C18—H18B···O19iv | 0.98 | 2.46 | 3.413 (2) | 165 |
Symmetry codes: (i) x+1/2, −y+3/2, −z; (ii) x−1/2, −y+3/2, −z; (iii) −x+3/2, −y+2, z−1/2; (iv) x−1/2, −y+5/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C18H21NO5 |
Mr | 331.36 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 90 |
a, b, c (Å) | 7.2080 (1), 12.7611 (3), 16.3676 (4) |
V (Å3) | 1505.52 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.22 × 0.20 × 0.15 |
Data collection | |
Diffractometer | Nonius KappaCCD area-detector diffractometer |
Absorption correction | Multi-scan (SCALEPACK; Otwinowski & Minor, 1997) |
Tmin, Tmax | 0.977, 0.984 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3445, 1988, 1746 |
Rint | 0.023 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.034, 0.081, 1.07 |
No. of reflections | 1988 |
No. of parameters | 220 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.21 |
Computer programs: COLLECT (Nonius, 1999), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELX97-2 (Sheldrick, 2008) and local procedures.
D—H···A | D—H | H···A | D···A | D—H···A |
O23—H23···O24 | 0.84 | 1.72 | 2.483 (2) | 150.6 |
C5—H5···O23i | 1.00 | 2.60 | 3.536 (2) | 156.8 |
C9—H9···O23ii | 1.00 | 2.36 | 3.314 (2) | 159.9 |
C16—H16B···O22iii | 0.99 | 2.40 | 3.227 (3) | 141.0 |
C18—H18B···O19iv | 0.98 | 2.46 | 3.413 (2) | 165.1 |
Symmetry codes: (i) x+1/2, −y+3/2, −z; (ii) x−1/2, −y+3/2, −z; (iii) −x+3/2, −y+2, z−1/2; (iv) x−1/2, −y+5/2, −z. |
Oxycodone is a semisynthetic codeine derivative that has been used as both an analgesic and an antitussive agent. In the mid-1990s, oxycontin was introduced as a slow-release formulation of oxycodone for use in patients with moderate to severe chronic pain associated with such ailments as arthritis, vertebral disc disease and cancer (Moore et al., 2003). Oxycodone metabolites excreted in the urine and faeces of several mammalian species, including man, have been reported (Ishida et al., 1982; Moore et al., 2003). There are seven known metabolites of oxycodone: oxycodone N-oxide, the title compound, (I), oxymorphone, (II), 6α-oxycodol, (III), 6β-oxycodol, (IV), 6α-oxycodol N-oxide, (V), noroxycodone, (VI), and 7β-hydroxy-6β-oxycodol, (VII) (see Scheme). In order to confirm the absolute stereochemistry of oxycodone N-oxide at the N-17 position, we synthesized (I) by the reaction of oxycodone with 3-chloroperbenzoic acid, employing nonaqueous solvents to afford an isomerically pure compound with subsequent crystallization of the product from chloroform. Depending on the orientation of the N—CH3 group, two diastereoisomers of oxycodone N-oxide are possible. However, in the present study we obtained exclusively a single diastereoisomer from NMR analysis of the product. To establish the orientation of N—CH3 in this synthetic N-oxide derivative of oxycodone, and to study the detailed conformation of this molecule, its X-ray structure determination was carried out and the results are presented here.
In an earlier study, a conformational analysis of several morphinan-6-one alkaloids was carried out using two-dimensional NMR techniques (Caldwell et al., 1993). In support of these NMR studies, X-ray crystallographic analysis of oxycodone N-oxide, (I), was also carried out. The present study of (I) and the Caldwell study are the same compound, but the X-ray analyses were undertaken at different temperatures, namely 90 and 293 K, respectively.
The numbering system of the non-H atoms and the overall configuration of the title compound are shown in Fig. 1, which shows that the absolute configuration of the chiral C centres in the molecule is identical to that of the starting material, oxycodone. The new chiral centre at position 17 is demonstrated to be R. The five-membered ring is distorted and the ethanamine ring has a typical chair conformation, with the newly formed N—O bond projected in an axial orientation. The conformation of the cyclohexanone ring is a twisted chair, which is caused by the presence of the 4,5-ether bridge, which is also responsible for the overall rigidity of the molecule. The observed C3—O19 [1.372 (2) Å] and O19—C20 [1.447 (2) Å] bond lengths are comparable with values found for methoxy O—CH3 bonds. There is an asymmetry of the exocyclic angles at C3 for (I) [O19—C3—C4 = 126.72 (19)° and O19—C3—C2 = 117.16 (16)°], as is typical of anisoles (Seip & Seip, 1973). This asymmetry of the angles at C3 is caused by the tendency of the methoxy group to be coplanar with the benzene ring, due to conjugation of the O19 lone pair with the benzene ring of (I), which is in agreement with earlier observations of a 4-methoxybenzyl group (Domiano et al., 1979). Most of the bond lengths and angles are in agreement with reported values (Caldwell et al., 1993), although values for the torsion angles are not available for comparison.
The X-ray structure of protonated oxymorphone, (II) (amine salt), has already been reported (Darling et al., 1982). We compared our results from (I) with these findings. Most of the bond lengths, bond angles and torsion angles for the non-H atoms of (I) are in agreement with the literature values for protonated (II). The C2—C3, C11—C12, C13—C5, C7—C8, C8—C14, C14—C9, C10—C11 and C15—C16 bonds are considerably longer (0.034–0.053 Å) in (I) compared with the values observed for protonated (II). Also, the N17—C9 bond longer by 0.037 Å. Comparison of bond angles for (I) and protonated (II) suggests that they are essentially very close, except for C9—C14—O23, which is larger by nearly 8°. This may be the result of strong intramolecular hydrogen bonding, resulting in some stretching of the molecule. This accounts for the increases in the above-mentioned bond lengths and bond angle. Furthermore, the C8—C14—C13—C5, C14—C13—C5—C6, C14—C13—C15—C16 and C13—C15—C16—N17 torsion angles are slightly larger than the values reported for protonated (II). Changes in some of the bond lengths, bond angles and torsion angles away from the site of the newly formed N—O bond suggest long-range substituent effects. The positive charge on the N atom also has an effect, which can be transmitted throughout the molecule via long-range inductive and electrostatic field effects.
The H atom attached to atom O23 is involved in an intramolecular hydrogen bond with atom O24 (Table 1). In addition, there are weak intermolecular C—H···O interactions (Table 1) which, along with van der Waals forces, stabilize the structure.