Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801001726/ob6025sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536801001726/ob6025Isup2.hkl |
CCDC reference: 159765
To prepare the title compound, (I), zinc dust (3.0 g, 325 mesh Aldrich) was added in several portions during 10 min to a boiling solution of androstenedione (500 mg, 1.75 mmol) in glacial acetic acid (30 ml) after which the reaction was complete (thin-layer chromatography control). The zinc suspension was filtered, the zinc was washed with glacial acetic acid and the filtrate was evaporated to dryness. The residue was diluted with water (100 ml) and extracted with diethyl ether (3 × 100 ml). The organic layers were washed with aqueous 10% NaHCO3 (3 × 100) ml and water (3 × 100 ml), dried (MgSO4) and evaporated to dryness to give a colourless crystalline solid (476 mg) composed by an isomeric mixture of 5α- and 5β-androst-3-en-17-one (70:30). Crystallization from methanol gave the pure 5α compound [(I); 285 mg, 1.05 mmol] in 60% yield; m.p. 398–399 K, literature 397–399 K (McKenna et al., 1959). Crystals of (I) suitable for X-ray experiments were obtained by slow evaporation of an n-hexane solution.
H atoms were placed at calculated positions and constrained as riding. The absolute configuration was chosen to give the correct chirality of the molecule that was known beforehand from the synthesis route (McKenna et al., 1959).
Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: PLATON (Spek, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.
Fig. 1. ORTEPII (Johnson, 1976) plot of (I). Displacement ellipsoids are drawn at the 50% probability level. | |
Fig. 2. Packing diagram of (I) viewed along the b axis. |
C19H28O | Dx = 1.147 Mg m−3 |
Mr = 272.41 | Melting point: 399 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
a = 6.451 (3) Å | Cell parameters from 25 reflections |
b = 9.2109 (9) Å | θ = 5.9–10.3° |
c = 26.558 (8) Å | µ = 0.07 mm−1 |
V = 1578.0 (10) Å3 | T = 293 K |
Z = 4 | Block, colourless |
F(000) = 600 | 0.50 × 0.45 × 0.30 mm |
Enraf-Nonius CAD-4 diffractometer | Rint = 0.048 |
Radiation source: fine-focus sealed tube | θmax = 27.5°, θmin = 3.1° |
Graphite monochromator | h = 0→8 |
profile data from ω–2θ scans | k = 0→11 |
3713 measured reflections | l = −34→34 |
2091 independent reflections | 3 standard reflections every 180 min |
1607 reflections with I > 2σ(I) | intensity decay: 1.4% |
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)] = 0.040 | H-atom parameters constrained |
wR(F2) = 0.109 | w = 1/[σ2(Fo2) + (0.0409P)2 + 0.3113P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max < 0.001 |
2091 reflections | Δρmax = 0.19 e Å−3 |
184 parameters | Δρmin = −0.14 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0101 (18) |
C19H28O | V = 1578.0 (10) Å3 |
Mr = 272.41 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.451 (3) Å | µ = 0.07 mm−1 |
b = 9.2109 (9) Å | T = 293 K |
c = 26.558 (8) Å | 0.50 × 0.45 × 0.30 mm |
Enraf-Nonius CAD-4 diffractometer | Rint = 0.048 |
3713 measured reflections | 3 standard reflections every 180 min |
2091 independent reflections | intensity decay: 1.4% |
1607 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.040 | 0 restraints |
wR(F2) = 0.109 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.19 e Å−3 |
2091 reflections | Δρmin = −0.14 e Å−3 |
184 parameters |
Experimental. νmax (KBr)/cm-1 3014 (C–H), 1737 (C═O); 1H NMR (500 MHz, CDCl3) δ: 0.80 (3H,s, 19-H3), 0.88 (3H, s, 18-H3), 5.29 (1H, ddd, J4,3 9.5, J4,5 3.8, J\{4,2\alpha\} 2.0, \{4-H\}), 5.57 (1H, ddd, J3,4 9.5, J\{3,2\beta\} 6.8, J\{3,2\alpha\} 3.2, \{3-H\}); 13C NMR (75.6 MHz, CDCl3) δ: 11.9 (C-19), 14.0 (C-18), 46.1 (C-5), 125.6 (C-3), 131.0 (C-4), 220.3 (C-17). |
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. Due to the absence of a strong enough anomalous scatterer at the Mo wavelength the absolute configuration could not be confirmed from the X-ray data. 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. Examination of the crystal structure with PLATON (Spek, 1995) showed that there are no solvent-accessible voids in the crystal lattice. All calculations were performed on a Pentium 350 MHz PC running LINUX. |
x | y | z | Uiso*/Ueq | ||
C10 | 0.6580 (3) | 0.2096 (2) | 0.14778 (8) | 0.0427 (5) | |
C9 | 0.6231 (3) | 0.3395 (2) | 0.11206 (7) | 0.0385 (5) | |
H9 | 0.7608 | 0.3811 | 0.1060 | 0.046* | |
C8 | 0.4948 (3) | 0.4618 (2) | 0.13743 (7) | 0.0393 (5) | |
H8 | 0.3571 | 0.4232 | 0.1454 | 0.047* | |
C14 | 0.4689 (3) | 0.5861 (2) | 0.10079 (8) | 0.0409 (5) | |
H14 | 0.6093 | 0.6185 | 0.0924 | 0.049* | |
O17 | 0.3318 (3) | 0.7081 (2) | −0.01963 (7) | 0.0666 (5) | |
C11 | 0.5378 (4) | 0.2990 (3) | 0.05997 (8) | 0.0529 (6) | |
H11A | 0.6332 | 0.2321 | 0.0439 | 0.063* | |
H11B | 0.4065 | 0.2491 | 0.0642 | 0.063* | |
C12 | 0.5052 (4) | 0.4294 (3) | 0.02541 (8) | 0.0529 (6) | |
H12A | 0.6381 | 0.4728 | 0.0173 | 0.063* | |
H12B | 0.4411 | 0.3978 | −0.0058 | 0.063* | |
C13 | 0.3683 (3) | 0.5408 (2) | 0.05079 (9) | 0.0425 (5) | |
C1 | 0.8088 (4) | 0.0984 (3) | 0.12457 (10) | 0.0603 (7) | |
H1A | 0.7487 | 0.0600 | 0.0938 | 0.072* | |
H1B | 0.9370 | 0.1472 | 0.1157 | 0.072* | |
C7 | 0.5983 (4) | 0.5102 (3) | 0.18674 (8) | 0.0545 (6) | |
H7A | 0.7290 | 0.5573 | 0.1791 | 0.065* | |
H7B | 0.5101 | 0.5805 | 0.2035 | 0.065* | |
C5 | 0.7657 (4) | 0.2681 (3) | 0.19566 (9) | 0.0517 (6) | |
H5 | 0.8918 | 0.3172 | 0.1841 | 0.062* | |
C6 | 0.6376 (4) | 0.3829 (3) | 0.22207 (9) | 0.0593 (7) | |
H6A | 0.7104 | 0.4166 | 0.2518 | 0.071* | |
H6B | 0.5064 | 0.3415 | 0.2327 | 0.071* | |
C15 | 0.3490 (4) | 0.7228 (2) | 0.11589 (9) | 0.0545 (6) | |
H15A | 0.4267 | 0.7807 | 0.1399 | 0.065* | |
H15B | 0.2151 | 0.6985 | 0.1302 | 0.065* | |
C17 | 0.3420 (4) | 0.6876 (3) | 0.02537 (9) | 0.0510 (6) | |
C16 | 0.3250 (4) | 0.8025 (3) | 0.06524 (10) | 0.0602 (7) | |
H16A | 0.1914 | 0.8506 | 0.0634 | 0.072* | |
H16B | 0.4333 | 0.8746 | 0.0612 | 0.072* | |
C19 | 0.4529 (4) | 0.1326 (3) | 0.16007 (10) | 0.0581 (7) | |
H19A | 0.4771 | 0.0587 | 0.1849 | 0.087* | |
H19B | 0.3982 | 0.0890 | 0.1300 | 0.087* | |
H19C | 0.3553 | 0.2019 | 0.1730 | 0.087* | |
C2 | 0.8573 (5) | −0.0278 (3) | 0.16035 (12) | 0.0771 (9) | |
H2A | 0.7473 | −0.0993 | 0.1579 | 0.093* | |
H2B | 0.9850 | −0.0739 | 0.1496 | 0.093* | |
C4 | 0.8364 (4) | 0.1486 (3) | 0.22969 (10) | 0.0643 (7) | |
H4 | 0.8508 | 0.1685 | 0.2638 | 0.077* | |
C3 | 0.8790 (5) | 0.0169 (3) | 0.21371 (13) | 0.0763 (9) | |
H3 | 0.9249 | −0.0515 | 0.2370 | 0.092* | |
C18 | 0.1442 (4) | 0.4843 (3) | 0.05704 (10) | 0.0573 (6) | |
H18A | 0.1442 | 0.4015 | 0.0789 | 0.086* | |
H18B | 0.0900 | 0.4571 | 0.0247 | 0.086* | |
H18C | 0.0593 | 0.5594 | 0.0713 | 0.086* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C10 | 0.0427 (11) | 0.0411 (10) | 0.0445 (11) | 0.0074 (11) | 0.0047 (10) | 0.0025 (10) |
C9 | 0.0371 (10) | 0.0419 (10) | 0.0366 (11) | −0.0005 (9) | 0.0036 (8) | −0.0015 (9) |
C8 | 0.0393 (11) | 0.0419 (11) | 0.0368 (10) | 0.0019 (10) | 0.0022 (9) | −0.0021 (9) |
C14 | 0.0398 (10) | 0.0392 (11) | 0.0438 (11) | −0.0015 (9) | −0.0001 (9) | −0.0023 (9) |
O17 | 0.0621 (11) | 0.0817 (12) | 0.0559 (10) | −0.0006 (12) | −0.0048 (9) | 0.0239 (10) |
C11 | 0.0679 (15) | 0.0473 (12) | 0.0434 (12) | 0.0098 (12) | −0.0031 (11) | −0.0102 (11) |
C12 | 0.0597 (14) | 0.0639 (15) | 0.0350 (11) | 0.0082 (13) | −0.0017 (11) | −0.0041 (11) |
C13 | 0.0380 (10) | 0.0476 (12) | 0.0419 (11) | −0.0019 (10) | −0.0023 (9) | 0.0027 (10) |
C1 | 0.0600 (15) | 0.0533 (14) | 0.0675 (17) | 0.0163 (13) | 0.0070 (13) | −0.0002 (13) |
C7 | 0.0661 (15) | 0.0548 (13) | 0.0428 (12) | 0.0099 (13) | −0.0057 (11) | −0.0125 (11) |
C5 | 0.0470 (12) | 0.0619 (15) | 0.0461 (13) | 0.0080 (12) | −0.0024 (10) | 0.0029 (12) |
C6 | 0.0651 (15) | 0.0713 (16) | 0.0414 (12) | 0.0161 (15) | −0.0062 (11) | −0.0055 (12) |
C15 | 0.0635 (14) | 0.0432 (11) | 0.0567 (14) | 0.0080 (13) | −0.0057 (13) | −0.0031 (11) |
C17 | 0.0383 (11) | 0.0587 (14) | 0.0560 (14) | −0.0028 (12) | −0.0028 (10) | 0.0145 (12) |
C16 | 0.0617 (15) | 0.0475 (12) | 0.0713 (17) | 0.0028 (13) | −0.0037 (13) | 0.0102 (12) |
C19 | 0.0553 (14) | 0.0516 (13) | 0.0675 (16) | −0.0047 (12) | 0.0032 (12) | 0.0098 (13) |
C2 | 0.0759 (18) | 0.0558 (16) | 0.100 (2) | 0.0239 (16) | 0.0069 (18) | 0.0109 (16) |
C4 | 0.0510 (14) | 0.0833 (19) | 0.0585 (15) | 0.0116 (15) | −0.0061 (12) | 0.0173 (15) |
C3 | 0.0649 (18) | 0.0768 (19) | 0.087 (2) | 0.0214 (17) | −0.0020 (16) | 0.0279 (18) |
C18 | 0.0432 (12) | 0.0585 (14) | 0.0703 (16) | −0.0097 (12) | −0.0073 (12) | 0.0062 (13) |
C10—C19 | 1.536 (3) | C12—C13 | 1.512 (3) |
C10—C1 | 1.542 (3) | C13—C17 | 1.520 (3) |
C10—C9 | 1.544 (3) | C13—C18 | 1.545 (3) |
C10—C5 | 1.546 (3) | C1—C2 | 1.533 (4) |
C9—C11 | 1.535 (3) | C7—C6 | 1.523 (3) |
C9—C8 | 1.552 (3) | C5—C4 | 1.496 (3) |
C8—C14 | 1.511 (3) | C5—C6 | 1.514 (3) |
C8—C7 | 1.536 (3) | C15—C16 | 1.540 (3) |
C14—C15 | 1.531 (3) | C17—C16 | 1.501 (4) |
C14—C13 | 1.536 (3) | C2—C3 | 1.482 (4) |
O17—C17 | 1.212 (3) | C4—C3 | 1.315 (4) |
C11—C12 | 1.526 (3) | ||
C19—C10—C1 | 108.74 (19) | C17—C13—C14 | 100.96 (18) |
C19—C10—C9 | 111.30 (18) | C12—C13—C18 | 111.4 (2) |
C1—C10—C9 | 111.19 (18) | C17—C13—C18 | 104.05 (18) |
C19—C10—C5 | 111.9 (2) | C14—C13—C18 | 113.20 (19) |
C1—C10—C5 | 106.08 (19) | C2—C1—C10 | 112.6 (2) |
C9—C10—C5 | 107.50 (18) | C6—C7—C8 | 112.0 (2) |
C11—C9—C10 | 114.68 (17) | C4—C5—C6 | 113.6 (2) |
C11—C9—C8 | 112.11 (17) | C4—C5—C10 | 112.2 (2) |
C10—C9—C8 | 111.93 (16) | C6—C5—C10 | 112.28 (19) |
C14—C8—C7 | 112.17 (18) | C5—C6—C7 | 110.0 (2) |
C14—C8—C9 | 109.21 (16) | C14—C15—C16 | 102.37 (19) |
C7—C8—C9 | 110.41 (18) | O17—C17—C16 | 125.6 (2) |
C8—C14—C15 | 120.66 (18) | O17—C17—C13 | 125.7 (2) |
C8—C14—C13 | 113.46 (17) | C16—C17—C13 | 108.75 (19) |
C15—C14—C13 | 103.65 (18) | C17—C16—C15 | 105.82 (19) |
C12—C11—C9 | 113.58 (18) | C3—C2—C1 | 113.7 (2) |
C13—C12—C11 | 110.26 (18) | C3—C4—C5 | 123.2 (3) |
C12—C13—C17 | 118.1 (2) | C4—C3—C2 | 123.0 (3) |
C12—C13—C14 | 108.83 (18) |
Experimental details
Crystal data | |
Chemical formula | C19H28O |
Mr | 272.41 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 6.451 (3), 9.2109 (9), 26.558 (8) |
V (Å3) | 1578.0 (10) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.50 × 0.45 × 0.30 |
Data collection | |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3713, 2091, 1607 |
Rint | 0.048 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.040, 0.109, 1.07 |
No. of reflections | 2091 |
No. of parameters | 184 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.19, −0.14 |
Computer programs: CAD-4 Software (Enraf-Nonius, 1989), CAD-4 Software, PLATON (Spek, 1995), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976), SHELXL97.
Following our work on several androstane derivatives (Andrade et al., 1999) as potential aromatase inhibitors and intermediates of their syntheses, the present study aims to contribute towards the elucidation of the different reactivities of the 5α- and 5β-androst-3-en-17-one, upon treatment with performic acid generated in situ in dichloromethane. The title compound, (I), was prepared from androst-4-ene-3,17-dione, through a modification of the McKenna process (McKenna et al., 1959), as starting material for the synthesis of the potent and clinically useful antitumor steroid 4-hydroxy-androst-4-ene-3,17-dione (Tavares da Silva et al., 1996) and its ring D modified derivative 4-hydroxy-17a-oxa-17a-homoandrost-4-ene-3,17-dione (Tavares da Silva et al., 1997; Paixão et al., 1998). The difference between the two epimers, 5α and 5β, is in the absolute configuration at C5. A 5β-isomer would have a cis junction of rings A and B, the rings are fused trans in a 5α-isomer. The X-ray analysis unequivocally establishes the molecular structure of (I) as an α configuration.
All ring junctions are trans (Fig. 1). The unsaturated ring A takes an intermediate conformation between 10β-sofa and 1α,10β half-chair [Cremer & Pople (1975) puckering parameters: Q = 0.508 (3) Å, θ = 50.3 (3)°, ϕ = 312.0 (4)°; Duax and Norton (1975) asymmetry parameters: ΔCs(3) = 9.6 (3)°, ΔC2(3,4) = 15.8 (4)° and ΔC2(1,2) = 51.7 (4)°]. Rings B and C have slightly flattened chair conformations, as shown by the mean values of their torsion angles [57 (2) and 55 (3)°, respectively]. Ring D assumes a 14α-envelope conformation with puckering parameters q2 = 0.422 (3) Å and ϕ2 = 214.1 (4)° [pseudo-rotation (Altona et al., 1968) and asymmetry parameters (Duax & Norton, 1975): Δ = -31.4 (4)°, ϕm = 43.2 (1)°, ΔCs(14) = 2.0 (2)°, ΔC2(13,14) = 18.5 (2)°]. The value of the pseudo-torsion angle C19—C10—C13—C18 of 0.01 (19)° shows that the molecule is not twisted. The dimension of the present steroid molecule may be measured by the distance between the C3 and O17 atoms, 9.560 (4) Å. The crystal structure contains no hydrogen bonds and thus cohesion is mainly achieved by van der Waals interactions (Fig. 2).