Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802023413/ac6027sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536802023413/ac60273sup2.hkl |
CCDC reference: 204670
Synthesis of 5-butylthebaine, (2): to a stirred solution of TMEDA (0.78 ml, 5.1 mmol) in dry tetrahydrofuran (THF, 10 ml), cooled to 195 K, was added a solution of BuLi solution (12 ml of a 1.11 M solution in hexane, 13.3 mmol). The mixture was stirred for 30 min before the slow addition of a solution of thebaine, (1) (0.93 g, 3.0 mmol) in dry THF (20 ml). The solution was allowed to stir at 195 K for 1 h, followed by the addition of N-bromosuccinimide (0.60 g, 3.4 mmol) in THF (10 ml). After stirring for a further 30 min at 195 K, the solution was allowed to come to room temperature over 2 h, and stirred at room temperature overnight. After removal of the solvent, the residue was taken up in CHCl3 (50 ml), washed with NaHCO3 solution, water, and brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on silica gel (gradient from 2% to 10% MeOH in CH2Cl2) to afford (2) (0.61 g, 55%) as a colorless foam as the sole product. 1H NMR (300 MHz, CDCl3): δ 0.90 (t, 3H, J = 6.6 Hz, CH3 in butyl group), 2.46 (s, NCH3), 3.29 (d, 1H, J = 18.3 Hz), 3.56 (s, 3H, OMe), 3.65 (d, 1H, J = 6.1 Hz), 3.83 (s, 3H, OMe), 5.07 (d, 1H, J = 6.4 Hz), 5.55 (d, 1H, J = 6.4 Hz), 6.57 (d, 1H, J = 8.3 Hz), 6.63 (d, 1H, J = 8.3 Hz).
Synthesis of 5-butylthevinone, (3): a mixture of (2) (0.56 g, 1.52 mmol), 3-buten-2-one (4.8 ml, 57.7 mmol) and toluene (10 ml) was heated under reflux for 13 d. The reaction mixture was concentrated, and the residue was purified by flash chromatography on silica gel (gradient: 1% to 3% MeOH in CH2Cl2) to afford (3) (0.28 g, 42%) as a colorless solid as the only product. Evaporative recrystallization from MeOH provided crystals suitable for X-ray analysis; m.p. 456–457 K. 1H NMR (300 MHz, CDCl3): δ 0.93 (t, 3H, J = 6.6 Hz, CH3 in butyl group), 2.14 (s, 3H, Me in acetyl), 2.34 (s, 3H, NMe), 3.11 (d, 1H, J = 6.4 Hz), 3.24 (d, 1H, J = 18.3 Hz), 3.58 (s, 3H, OMe), 3.82 (s, 3H, OMe), 5.48 (d, 1H, J = 8.8 Hz), 5.97 (d, 1H, J = 8.8 Hz), 6.47 (d, 1H, J = 8.0 Hz), 6.61 (d, 1H, J = 8.0 Hz). 13C NMR (75 MHz, CDCl3): δ 210.10, 148.64, 141.65, 135.99, 129.29, 125.32, 119.14, 115.09, 100.34, 84.04, 60.88, 57.74, 54.86, 50.53, 49.69, 45.97, 44.83, 43.73, 32.25, 29.24 (2 C), 29.11, 28.92, 27.66, 24.16, 23.13, 14.49. EIMS m/z: 437 (M+, 47%), 394 (32%), 206 (100%).
The β-butyl side chain off C5 can also be modeled with a disorder of atoms C5B, C5C and C5D. Including this disorder also requires distance constraints on the C5C—C5D bond in the major component and the C5B'—C5C' and C5C'—C5D' distances in the minor component, and the anisotropic displacement parameters for C5B', C5C' and C5D'. The minor component had an occupancy of 30% or less and peaks in the final difference map were still in the area of this disordered side chain indicating the disorder may be even more complex (i.e. over more than the two positions modeled). Due to problems with modeling of the disorder this was omitted from the final refinement.
Data collection: SMART (Bruker, 1999); cell refinement: SMART; data reduction: SAINT (Bruker, 2000) and XPREP (Bruker, 1997); program(s) used to solve structure: SHELXTL (Bruker, 2000); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
C27H35NO4 | F(000) = 472 |
Mr = 437.56 | Dx = 1.251 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.706 (5) Å | Cell parameters from 1983 reflections |
b = 7.292 (3) Å | θ = 2.5–23.7° |
c = 16.958 (8) Å | µ = 0.08 mm−1 |
β = 104.519 (6)° | T = 298 K |
V = 1161.8 (9) Å3 | Prism, colorless |
Z = 2 | 0.64 × 0.18 × 0.06 mm |
Bruker SMART 1000 CCD diffractometer | 3701 independent reflections |
Radiation source: sealed tube | 2014 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.056 |
ϕ and ω scans | θmax = 28.4°, θmin = 2.2° |
Absorption correction: multi-scan (Bruker, 2000) | h = −12→12 |
Tmin = 0.921, Tmax = 0.994 | k = −3→9 |
5557 measured reflections | l = −20→22 |
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)] = 0.056 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.124 | H-atom parameters constrained |
S = 0.97 | w = 1/[σ2(Fo2) + (0.0467P)2] where P = (Fo2 + 2Fc2)/3 |
3701 reflections | (Δ/σ)max < 0.001 |
290 parameters | Δρmax = 0.29 e Å−3 |
2 restraints | Δρmin = −0.25 e Å−3 |
C27H35NO4 | V = 1161.8 (9) Å3 |
Mr = 437.56 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 9.706 (5) Å | µ = 0.08 mm−1 |
b = 7.292 (3) Å | T = 298 K |
c = 16.958 (8) Å | 0.64 × 0.18 × 0.06 mm |
β = 104.519 (6)° |
Bruker SMART 1000 CCD diffractometer | 3701 independent reflections |
Absorption correction: multi-scan (Bruker, 2000) | 2014 reflections with I > 2σ(I) |
Tmin = 0.921, Tmax = 0.994 | Rint = 0.056 |
5557 measured reflections |
R[F2 > 2σ(F2)] = 0.056 | 2 restraints |
wR(F2) = 0.124 | H-atom parameters constrained |
S = 0.97 | Δρmax = 0.29 e Å−3 |
3701 reflections | Δρmin = −0.25 e Å−3 |
290 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 | ||
C1 | −0.1834 (4) | 0.8561 (6) | 0.1632 (2) | 0.0501 (11) | |
H1A | −0.2769 | 0.8731 | 0.1662 | 0.060* | |
C2 | −0.1304 (4) | 0.9586 (5) | 0.1077 (2) | 0.0507 (12) | |
H2A | −0.1916 | 1.0360 | 0.0715 | 0.061* | |
C3 | 0.0102 (4) | 0.9479 (5) | 0.1053 (2) | 0.0448 (10) | |
O3 | 0.0594 (3) | 1.0706 (4) | 0.05736 (15) | 0.0603 (8) | |
C3A | 0.1397 (4) | 0.9919 (6) | 0.0052 (2) | 0.0650 (14) | |
H3AA | 0.1705 | 1.0875 | −0.0254 | 0.097* | |
H3AB | 0.0811 | 0.9067 | −0.0316 | 0.097* | |
H3AC | 0.2213 | 0.9291 | 0.0377 | 0.097* | |
C4 | 0.0952 (4) | 0.8220 (5) | 0.15682 (19) | 0.0389 (9) | |
O5 | 0.2407 (2) | 0.8124 (3) | 0.17438 (13) | 0.0418 (7) | |
C5 | 0.2887 (4) | 0.6691 (5) | 0.2377 (2) | 0.0388 (10) | |
C5A | 0.3854 (4) | 0.5432 (6) | 0.20240 (19) | 0.0497 (11) | |
H5AA | 0.4803 | 0.5958 | 0.2159 | 0.060* | |
H5AB | 0.3914 | 0.4259 | 0.2300 | 0.060* | |
C5B | 0.3436 (5) | 0.5085 (7) | 0.1131 (2) | 0.0768 (15) | |
H5BA | 0.3559 | 0.6216 | 0.0856 | 0.092* | |
H5BB | 0.2430 | 0.4788 | 0.0978 | 0.092* | |
C5C | 0.4219 (6) | 0.3599 (11) | 0.0818 (3) | 0.141 (3) | |
H5CA | 0.3972 | 0.2433 | 0.1022 | 0.169* | |
H5CB | 0.3889 | 0.3570 | 0.0229 | 0.169* | |
C5D | 0.5773 (6) | 0.3772 (14) | 0.1037 (4) | 0.179 (4) | |
H5DA | 0.6186 | 0.2685 | 0.0873 | 0.268* | |
H5DB | 0.6109 | 0.3927 | 0.1615 | 0.268* | |
H5DC | 0.6042 | 0.4818 | 0.0765 | 0.268* | |
C6 | 0.3720 (4) | 0.7631 (5) | 0.3188 (2) | 0.0381 (10) | |
O6 | 0.5064 (3) | 0.8377 (4) | 0.31458 (15) | 0.0506 (7) | |
C6A | 0.5060 (5) | 1.0042 (7) | 0.2724 (3) | 0.0788 (15) | |
H6AA | 0.6018 | 1.0371 | 0.2727 | 0.118* | |
H6AB | 0.4648 | 1.0988 | 0.2986 | 0.118* | |
H6AC | 0.4509 | 0.9901 | 0.2172 | 0.118* | |
C7 | 0.4064 (4) | 0.6017 (5) | 0.38347 (18) | 0.0386 (10) | |
H7A | 0.4453 | 0.4990 | 0.3586 | 0.046* | |
C7A | 0.5211 (4) | 0.6634 (5) | 0.4592 (2) | 0.0416 (10) | |
O7 | 0.4881 (3) | 0.7283 (4) | 0.51700 (16) | 0.0590 (8) | |
C7B | 0.6712 (4) | 0.6286 (6) | 0.4587 (2) | 0.0549 (12) | |
H7BA | 0.7328 | 0.6730 | 0.5084 | 0.082* | |
H7BB | 0.6924 | 0.6909 | 0.4133 | 0.082* | |
H7BC | 0.6856 | 0.4992 | 0.4539 | 0.082* | |
C8 | 0.2695 (3) | 0.5362 (6) | 0.4037 (2) | 0.0432 (10) | |
H8A | 0.2702 | 0.5710 | 0.4590 | 0.052* | |
H8B | 0.2633 | 0.4036 | 0.3998 | 0.052* | |
C9 | −0.0051 (4) | 0.5484 (6) | 0.3501 (2) | 0.0433 (10) | |
H9A | −0.0133 | 0.5733 | 0.4055 | 0.052* | |
C10 | −0.1331 (4) | 0.6490 (5) | 0.2890 (2) | 0.0481 (11) | |
H10A | −0.2105 | 0.5621 | 0.2717 | 0.058* | |
H10B | −0.1667 | 0.7469 | 0.3181 | 0.058* | |
C11 | −0.0981 (4) | 0.7295 (5) | 0.2140 (2) | 0.0413 (10) | |
C12 | 0.0356 (4) | 0.7049 (5) | 0.20308 (19) | 0.0371 (10) | |
C13 | 0.1514 (4) | 0.5857 (5) | 0.25500 (18) | 0.0361 (9) | |
C14 | 0.1394 (4) | 0.6238 (5) | 0.34323 (19) | 0.0371 (9) | |
C15 | 0.1294 (4) | 0.3795 (5) | 0.2355 (2) | 0.0497 (11) | |
H15A | 0.1211 | 0.3611 | 0.1779 | 0.060* | |
H15B | 0.2129 | 0.3131 | 0.2653 | 0.060* | |
C16 | −0.0018 (4) | 0.2991 (6) | 0.2569 (2) | 0.0543 (12) | |
H16A | −0.0870 | 0.3446 | 0.2190 | 0.065* | |
H16B | −0.0007 | 0.1666 | 0.2520 | 0.065* | |
N17 | −0.0050 (3) | 0.3488 (5) | 0.33974 (18) | 0.0479 (9) | |
C17 | −0.1207 (5) | 0.2576 (6) | 0.3647 (3) | 0.0739 (14) | |
H17A | −0.1159 | 0.1280 | 0.3559 | 0.111* | |
H17B | −0.2102 | 0.3041 | 0.3332 | 0.111* | |
H17C | −0.1123 | 0.2807 | 0.4214 | 0.111* | |
C18 | 0.1592 (4) | 0.8259 (5) | 0.35837 (19) | 0.0430 (10) | |
H18A | 0.0918 | 0.8969 | 0.3748 | 0.052* | |
C19 | 0.2770 (4) | 0.8971 (5) | 0.34719 (19) | 0.0385 (10) | |
H19A | 0.2999 | 1.0205 | 0.3561 | 0.046* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.033 (2) | 0.057 (3) | 0.052 (2) | 0.010 (2) | −0.0042 (19) | −0.013 (2) |
C2 | 0.055 (3) | 0.048 (3) | 0.041 (2) | 0.015 (2) | −0.001 (2) | −0.005 (2) |
C3 | 0.057 (3) | 0.038 (3) | 0.036 (2) | 0.004 (2) | 0.0044 (19) | 0.0036 (19) |
O3 | 0.080 (2) | 0.0472 (19) | 0.0531 (16) | 0.0137 (17) | 0.0152 (15) | 0.0109 (15) |
C3A | 0.084 (3) | 0.061 (3) | 0.050 (2) | 0.003 (3) | 0.018 (2) | 0.009 (2) |
C4 | 0.045 (2) | 0.039 (2) | 0.0292 (18) | 0.006 (2) | 0.0020 (16) | −0.0055 (18) |
O5 | 0.0386 (15) | 0.0469 (18) | 0.0380 (13) | 0.0068 (13) | 0.0059 (11) | 0.0080 (12) |
C5 | 0.041 (2) | 0.041 (3) | 0.033 (2) | 0.0052 (19) | 0.0077 (17) | 0.0040 (18) |
C5A | 0.049 (2) | 0.057 (3) | 0.041 (2) | 0.011 (2) | 0.0076 (18) | −0.001 (2) |
C5B | 0.099 (4) | 0.079 (4) | 0.056 (3) | 0.017 (3) | 0.026 (3) | −0.003 (3) |
C5C | 0.153 (6) | 0.178 (7) | 0.078 (4) | 0.055 (6) | 0.004 (4) | −0.033 (4) |
C5D | 0.101 (5) | 0.280 (12) | 0.158 (6) | 0.012 (7) | 0.037 (5) | −0.064 (8) |
C6 | 0.034 (2) | 0.039 (3) | 0.040 (2) | 0.0006 (19) | 0.0060 (17) | 0.0047 (18) |
O6 | 0.0414 (15) | 0.0484 (18) | 0.0605 (16) | −0.0028 (14) | 0.0100 (12) | 0.0131 (15) |
C6A | 0.072 (3) | 0.070 (4) | 0.099 (3) | −0.012 (3) | 0.030 (3) | 0.031 (3) |
C7 | 0.042 (2) | 0.036 (2) | 0.0330 (19) | 0.0030 (19) | 0.0011 (16) | −0.0001 (17) |
C7A | 0.045 (2) | 0.036 (3) | 0.039 (2) | 0.0013 (19) | 0.0016 (18) | 0.0006 (18) |
O7 | 0.0581 (17) | 0.069 (2) | 0.0460 (17) | 0.0038 (17) | 0.0053 (14) | −0.0138 (16) |
C7B | 0.041 (2) | 0.073 (3) | 0.048 (2) | 0.008 (2) | 0.0076 (18) | 0.000 (2) |
C8 | 0.046 (2) | 0.044 (3) | 0.036 (2) | −0.001 (2) | 0.0043 (17) | 0.0038 (19) |
C9 | 0.040 (2) | 0.047 (3) | 0.042 (2) | 0.006 (2) | 0.0082 (17) | 0.002 (2) |
C10 | 0.040 (2) | 0.050 (3) | 0.053 (2) | 0.001 (2) | 0.0102 (18) | −0.007 (2) |
C11 | 0.038 (2) | 0.042 (3) | 0.040 (2) | −0.001 (2) | 0.0017 (18) | −0.0087 (19) |
C12 | 0.039 (2) | 0.039 (3) | 0.0299 (19) | 0.003 (2) | 0.0021 (17) | −0.0057 (17) |
C13 | 0.039 (2) | 0.035 (2) | 0.0328 (19) | 0.0021 (18) | 0.0059 (16) | −0.0002 (17) |
C14 | 0.037 (2) | 0.035 (3) | 0.036 (2) | 0.0017 (18) | 0.0035 (16) | −0.0031 (17) |
C15 | 0.053 (2) | 0.047 (3) | 0.046 (2) | 0.008 (2) | 0.008 (2) | −0.006 (2) |
C16 | 0.054 (3) | 0.038 (3) | 0.067 (3) | −0.002 (2) | 0.007 (2) | −0.008 (2) |
N17 | 0.046 (2) | 0.042 (2) | 0.058 (2) | −0.0088 (17) | 0.0164 (16) | 0.0017 (17) |
C17 | 0.071 (3) | 0.051 (3) | 0.102 (4) | −0.009 (3) | 0.025 (3) | 0.004 (3) |
C18 | 0.053 (2) | 0.041 (3) | 0.0324 (19) | 0.007 (2) | 0.0069 (18) | −0.0019 (18) |
C19 | 0.045 (2) | 0.028 (2) | 0.040 (2) | −0.004 (2) | 0.0067 (18) | 0.0049 (17) |
C1—C11 | 1.386 (5) | C7—C7A | 1.541 (5) |
C1—C2 | 1.397 (5) | C7—C8 | 1.530 (4) |
C1—H1A | 0.9300 | C7—H7A | 0.9800 |
C2—C3 | 1.378 (5) | C7A—O7 | 1.201 (4) |
C2—H2A | 0.9300 | C7A—C7B | 1.481 (5) |
C3—O3 | 1.373 (4) | C7B—H7BA | 0.9600 |
C3—C4 | 1.387 (5) | C7B—H7BB | 0.9600 |
O3—C3A | 1.437 (4) | C7B—H7BC | 0.9600 |
C3A—H3AA | 0.9600 | C8—C14 | 1.551 (5) |
C3A—H3AB | 0.9600 | C8—H8A | 0.9700 |
C3A—H3AC | 0.9600 | C8—H8B | 0.9700 |
C4—O5 | 1.370 (4) | C9—N17 | 1.466 (5) |
C4—C12 | 1.381 (5) | C9—C14 | 1.537 (5) |
O5—C5 | 1.487 (4) | C9—C10 | 1.584 (5) |
C5—C5A | 1.537 (5) | C9—H9A | 0.9800 |
C5—C13 | 1.559 (5) | C10—C11 | 1.516 (5) |
C5—C6 | 1.569 (5) | C10—H10A | 0.9700 |
C5A—C5B | 1.488 (5) | C10—H10B | 0.9700 |
C5A—H5AA | 0.9700 | C11—C12 | 1.367 (5) |
C5A—H5AB | 0.9700 | C12—C13 | 1.516 (5) |
C5B—C5C | 1.495 (7) | C13—C15 | 1.543 (6) |
C5B—H5BA | 0.9700 | C13—C14 | 1.555 (4) |
C5B—H5BB | 0.9700 | C14—C18 | 1.501 (5) |
C5C—C5D | 1.466 (4) | C15—C16 | 1.527 (5) |
C5C—H5CA | 0.9700 | C15—H15A | 0.9700 |
C5C—H5CB | 0.9700 | C15—H15B | 0.9700 |
C5D—H5DA | 0.9600 | C16—N17 | 1.458 (5) |
C5D—H5DB | 0.9600 | C16—H16A | 0.9700 |
C5D—H5DC | 0.9600 | C16—H16B | 0.9700 |
C6—O6 | 1.432 (4) | N17—C17 | 1.456 (5) |
C6—C19 | 1.502 (5) | C17—H17A | 0.9600 |
C6—C7 | 1.586 (5) | C17—H17B | 0.9600 |
O6—C6A | 1.408 (5) | C17—H17C | 0.9600 |
C6A—H6AA | 0.9600 | C18—C19 | 1.312 (5) |
C6A—H6AB | 0.9600 | C18—H18A | 0.9300 |
C6A—H6AC | 0.9600 | C19—H19A | 0.9300 |
C11—C1—C2 | 120.8 (3) | C7B—C7A—C7 | 116.7 (3) |
C11—C1—H1A | 119.6 | C7A—C7B—H7BA | 109.5 |
C2—C1—H1A | 119.6 | C7A—C7B—H7BB | 109.5 |
C3—C2—C1 | 121.6 (4) | H7BA—C7B—H7BB | 109.5 |
C3—C2—H2A | 119.2 | C7A—C7B—H7BC | 109.5 |
C1—C2—H2A | 119.2 | H7BA—C7B—H7BC | 109.5 |
O3—C3—C2 | 118.3 (3) | H7BB—C7B—H7BC | 109.5 |
O3—C3—C4 | 124.4 (4) | C7—C8—C14 | 109.4 (3) |
C2—C3—C4 | 117.1 (4) | C7—C8—H8A | 109.8 |
C3—O3—C3A | 115.3 (3) | C14—C8—H8A | 109.8 |
O3—C3A—H3AA | 109.5 | C7—C8—H8B | 109.8 |
O3—C3A—H3AB | 109.5 | C14—C8—H8B | 109.8 |
H3AA—C3A—H3AB | 109.5 | H8A—C8—H8B | 108.2 |
O3—C3A—H3AC | 109.5 | N17—C9—C14 | 108.5 (3) |
H3AA—C3A—H3AC | 109.5 | N17—C9—C10 | 113.9 (3) |
H3AB—C3A—H3AC | 109.5 | C14—C9—C10 | 111.4 (3) |
O5—C4—C12 | 113.6 (3) | N17—C9—H9A | 107.6 |
O5—C4—C3 | 126.0 (4) | C14—C9—H9A | 107.6 |
C12—C4—C3 | 120.0 (3) | C10—C9—H9A | 107.6 |
C4—O5—C5 | 108.2 (3) | C11—C10—C9 | 115.1 (3) |
O5—C5—C5A | 104.5 (3) | C11—C10—H10A | 108.5 |
O5—C5—C13 | 106.4 (3) | C9—C10—H10A | 108.5 |
C5A—C5—C13 | 118.4 (3) | C11—C10—H10B | 108.5 |
O5—C5—C6 | 109.0 (3) | C9—C10—H10B | 108.5 |
C5A—C5—C6 | 111.8 (3) | H10A—C10—H10B | 107.5 |
C13—C5—C6 | 106.4 (3) | C12—C11—C1 | 116.3 (4) |
C5B—C5A—C5 | 117.4 (3) | C12—C11—C10 | 118.8 (3) |
C5B—C5A—H5AA | 107.9 | C1—C11—C10 | 123.7 (3) |
C5—C5A—H5AA | 107.9 | C11—C12—C4 | 122.8 (4) |
C5B—C5A—H5AB | 107.9 | C11—C12—C13 | 126.0 (3) |
C5—C5A—H5AB | 107.9 | C4—C12—C13 | 109.2 (3) |
H5AA—C5A—H5AB | 107.2 | C12—C13—C15 | 113.1 (3) |
C5A—C5B—C5C | 116.9 (4) | C12—C13—C14 | 103.5 (3) |
C5A—C5B—H5BA | 108.1 | C15—C13—C14 | 109.9 (3) |
C5C—C5B—H5BA | 108.1 | C12—C13—C5 | 102.2 (3) |
C5A—C5B—H5BB | 108.1 | C15—C13—C5 | 114.7 (3) |
C5C—C5B—H5BB | 108.1 | C14—C13—C5 | 112.7 (3) |
H5BA—C5B—H5BB | 107.3 | C18—C14—C9 | 114.8 (3) |
C5D—C5C—C5B | 115.5 (6) | C18—C14—C8 | 104.1 (3) |
C5D—C5C—H5CA | 108.4 | C9—C14—C8 | 114.2 (3) |
C5B—C5C—H5CA | 108.4 | C18—C14—C13 | 107.6 (3) |
C5D—C5C—H5CB | 108.4 | C9—C14—C13 | 107.4 (3) |
C5B—C5C—H5CB | 108.4 | C8—C14—C13 | 108.5 (3) |
H5CA—C5C—H5CB | 107.5 | C16—C15—C13 | 113.7 (3) |
C5C—C5D—H5DA | 109.5 | C16—C15—H15A | 108.8 |
C5C—C5D—H5DB | 109.5 | C13—C15—H15A | 108.8 |
H5DA—C5D—H5DB | 109.5 | C16—C15—H15B | 108.8 |
C5C—C5D—H5DC | 109.5 | C13—C15—H15B | 108.8 |
H5DA—C5D—H5DC | 109.5 | H15A—C15—H15B | 107.7 |
H5DB—C5D—H5DC | 109.5 | N17—C16—C15 | 110.7 (3) |
O6—C6—C19 | 114.1 (3) | N17—C16—H16A | 109.5 |
O6—C6—C5 | 113.4 (3) | C15—C16—H16A | 109.5 |
C19—C6—C5 | 110.0 (3) | N17—C16—H16B | 109.5 |
O6—C6—C7 | 106.3 (3) | C15—C16—H16B | 109.5 |
C19—C6—C7 | 107.5 (3) | H16A—C16—H16B | 108.1 |
C5—C6—C7 | 104.8 (3) | C17—N17—C16 | 111.7 (3) |
C6A—O6—C6 | 117.8 (3) | C17—N17—C9 | 113.2 (3) |
O6—C6A—H6AA | 109.5 | C16—N17—C9 | 111.3 (3) |
O6—C6A—H6AB | 109.5 | N17—C17—H17A | 109.5 |
H6AA—C6A—H6AB | 109.5 | N17—C17—H17B | 109.5 |
O6—C6A—H6AC | 109.5 | H17A—C17—H17B | 109.5 |
H6AA—C6A—H6AC | 109.5 | N17—C17—H17C | 109.5 |
H6AB—C6A—H6AC | 109.5 | H17A—C17—H17C | 109.5 |
C7A—C7—C8 | 113.0 (3) | H17B—C17—H17C | 109.5 |
C7A—C7—C6 | 110.0 (3) | C19—C18—C14 | 116.3 (4) |
C8—C7—C6 | 110.0 (3) | C19—C18—H18A | 121.9 |
C7A—C7—H7A | 107.9 | C14—C18—H18A | 121.9 |
C8—C7—H7A | 107.9 | C18—C19—C6 | 114.6 (3) |
C6—C7—H7A | 107.9 | C18—C19—H19A | 122.7 |
O7—C7A—C7B | 122.4 (3) | C6—C19—H19A | 122.7 |
O7—C7A—C7 | 120.7 (3) |
Experimental details
Crystal data | |
Chemical formula | C27H35NO4 |
Mr | 437.56 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 298 |
a, b, c (Å) | 9.706 (5), 7.292 (3), 16.958 (8) |
β (°) | 104.519 (6) |
V (Å3) | 1161.8 (9) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.64 × 0.18 × 0.06 |
Data collection | |
Diffractometer | Bruker SMART 1000 CCD diffractometer |
Absorption correction | Multi-scan (Bruker, 2000) |
Tmin, Tmax | 0.921, 0.994 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5557, 3701, 2014 |
Rint | 0.056 |
(sin θ/λ)max (Å−1) | 0.670 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.056, 0.124, 0.97 |
No. of reflections | 3701 |
No. of parameters | 290 |
No. of restraints | 2 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.29, −0.25 |
Computer programs: SMART (Bruker, 1999), SMART, SAINT (Bruker, 2000) and XPREP (Bruker, 1997), SHELXTL (Bruker, 2000), SHELXTL.
The orvinols are an important class of opioids which are of continued interest due to their high potency as analgesics (Casy & Parfitt, 1986; Maat et al., 1999; Coop et al., 2000; Derrick et al., 2000; Meada & Coop, 2001). The preparation of the orvinols involves a Diels–Alder addition of a dienophile to the diene system of thebaine, (1), which occurs from the least hindered β-face (endo-adducts). Several reports have shown that the introduction of small substituents into the 5-position of thebaine (Boden et al., 1982) hinders the β-face to attack, giving rise to a small quantity of the adduct arising from attack from the α-face (exo-adducts) (Woudenberg et al., 1992, 1994; Baas et al., 1997; Maat et al., 1999). In an attempt to brominate the 5-position of thebaine, we inadvertently obtained the 5β-butylated derivative, (2), and considered that this compound would possess greater steric hindrance than the small substituents already investigated. We hypothesized that a greater quantity of the exo-adduct would result.
As expected a slow reaction was observed, but unexpectedly the only product formed was the endo-adduct, (3), resulting from attack from the β-face. Thus, the introduction of a large β-butyl group does not favor attack from the α-face.
The title compound, (3), crystallized in the monoclinic space group P21 with one molecule in the asymmetric unit (Fig. 1). The absolute configuration could not be determined from the X-ray data and was therefore set based on heroin (Deschamps et al., 1996).