organic compounds
Westphalen's diol diacetate: 19(10→5)-abeo-5β-cholest-9-ene-3β,6β-diyl diacetate
aBenemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Ciudad Universitaria, Puebla, Pue. 72570, Mexico, and bUniversidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, Nuevo León CP 66451, Mexico
*Correspondence e-mail: sylvain_bernes@hotmail.com
The structure of the title steroid [alternative name: 3β,6β-diacetoxy-5β-methyl-19-norcholest-9(10)-ene], C31H50O4, confirms the generally accepted mechanism for the rearrangement of a cholestan-5α-ol derivative reported a century ago by Westphalen. The methyl group at position 10 of the starting material migrates to position 5 in the steroidal nucleus, while a Δ9 bond is formed, as indicated by the C=C bond length of 1.347 (4) Å. The methyl transposition leaves the 5R configuration unchanged, with the methyl oriented towards the β face. During the rearrangement, the steroidal B ring experiences a conformational distortion from chair to envelope with the C atom at position 6 as the flap. In the title structure, the isopropyl group of the side chain is disordered over two positions, with occupancies of 0.733 (10) and 0.267 (10). The carbonyl O atom in the acetyl group at C3 is also disordered with an occupancy ratio of 0.62 (4):0.38 (4).
Related literature
For the initial report on the Westphalen rearrangement, see: Westphalen (1915). For applications in steroid synthesis, see: Rodig et al. (1961); Knights & Hanson (2004); Pinto et al. (2008, 2009). For mechanistic aspects of this rearrangement, see: Kočovský & Černý (1977); Kočovský et al. (1979); Kamernitskii et al. (1987).
Experimental
Crystal data
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Data collection: XSCANS (Siemens, 1996); cell XSCANS; data reduction: XSCANS; 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: SHELXL97.
Supporting information
10.1107/S1600536812045278/ff2087sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536812045278/ff2087Isup2.hkl
5-Hydroxy-5α-cholestane-3β,6β-diyl diacetate (6.1 g, 12.09 mmol) was treated with acetic anhydride (150 ml) for 20 min at 363 K. Then, NaHSO4 was added (1.74 g, 12.78 mmol) and stirred until complete consumption of the starting material (ca. 30 min). The mixture was poured in a 500 ml Erlenmeyer with pyridine and ice and vigorously stirred. The product, which deposited on the glass vessel, was dissolved in ethyl acetate, and then washed with saline solution, 5% HCl, distilled water, and finally 10% NaHCO3. This phase was dried over Na2SO4, and the solvent evaporated under reduced pressure. The crude (80% yield) was chromatographed over silicagel with petroleum ether and ethyl acetate (95:5) and crystallized from ethyl acetate. When KHSO4 was used, the Westphalen compound was obtained in 35% yield.
The isopropyl group in the lateral chain was found to be disordered over two positions, C251/C261/C271 and C252/C262/C272, and occupancies converged to 0.733 (10) and 0.267 (10), respectively. Both parts were restrained to have similar displacement parameters and geometry (SIMU and SAME restraints; Sheldrick, 2008). On the other side of the molecule, the carbonyl O atom in the acetyl group at C3 is also disordered over two sites, O301 and O302, with occupancies 0.62 (4) and 0.38 (4). All H atoms were placed in calculated positions and refined as riding to their carrier C atoms. C—H bond lengths were set to 0.96 (methyl) 0.97 (methylene) or 0.98 Å (methine), and isotropic parameters for H atoms were calculated as Uiso(H) = xUeq(carrier C) with x = 1.5 (methyl) or x = 1.2 (methylene and methine groups). Friedel pairs (714) were merged, and
assigned by fixing the configuration of known chiral centers.Data collection: XSCANS (Siemens, 1996); cell
XSCANS (Siemens, 1996); data reduction: XSCANS (Siemens, 1996); 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: SHELXL97 (Sheldrick, 2008).Fig. 1. ORTEP view of the title molecule, with displacement ellipsoids for non-H atoms at the 30% probability level. For disordered parts, sites with occupancy less than 0.5 have been omitted. |
C31H50O4 | Dx = 1.083 Mg m−3 |
Mr = 486.71 | Melting point: 393 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 70 reflections |
a = 9.2846 (15) Å | θ = 4.4–12.6° |
b = 10.7203 (18) Å | µ = 0.07 mm−1 |
c = 29.982 (4) Å | T = 298 K |
V = 2984.2 (8) Å3 | Prism, colourless |
Z = 4 | 0.6 × 0.5 × 0.5 mm |
F(000) = 1072 |
Siemens P4 diffractometer | Rint = 0.043 |
Radiation source: fine-focus sealed tube | θmax = 26.2°, θmin = 2.0° |
Graphite monochromator | h = −11→1 |
ω scans | k = −13→1 |
4350 measured reflections | l = −37→1 |
3393 independent reflections | 3 standard reflections every 97 reflections |
2827 reflections with I > 2σ(I) | intensity decay: 0.5% |
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)] = 0.048 | H-atom parameters constrained |
wR(F2) = 0.136 | w = 1/[σ2(Fo2) + (0.0701P)2 + 0.3625P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max < 0.001 |
3393 reflections | Δρmax = 0.14 e Å−3 |
364 parameters | Δρmin = −0.13 e Å−3 |
57 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 constraints | Extinction coefficient: 0.0087 (15) |
Primary atom site location: structure-invariant direct methods |
C31H50O4 | V = 2984.2 (8) Å3 |
Mr = 486.71 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 9.2846 (15) Å | µ = 0.07 mm−1 |
b = 10.7203 (18) Å | T = 298 K |
c = 29.982 (4) Å | 0.6 × 0.5 × 0.5 mm |
Siemens P4 diffractometer | Rint = 0.043 |
4350 measured reflections | 3 standard reflections every 97 reflections |
3393 independent reflections | intensity decay: 0.5% |
2827 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.048 | 57 restraints |
wR(F2) = 0.136 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.14 e Å−3 |
3393 reflections | Δρmin = −0.13 e Å−3 |
364 parameters |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
C1 | 0.2670 (3) | 0.4760 (3) | 0.61696 (10) | 0.0641 (7) | |
H1A | 0.2466 | 0.5401 | 0.5950 | 0.077* | |
H1B | 0.1814 | 0.4648 | 0.6351 | 0.077* | |
C2 | 0.3009 (4) | 0.3544 (3) | 0.59299 (9) | 0.0726 (8) | |
H2A | 0.2187 | 0.3299 | 0.5751 | 0.087* | |
H2B | 0.3821 | 0.3670 | 0.5731 | 0.087* | |
C3 | 0.3362 (3) | 0.2514 (3) | 0.62582 (9) | 0.0650 (7) | |
H3A | 0.3650 | 0.1761 | 0.6096 | 0.078* | |
C4 | 0.4562 (3) | 0.2908 (3) | 0.65690 (9) | 0.0606 (7) | |
H4A | 0.5454 | 0.2912 | 0.6401 | 0.073* | |
H4B | 0.4656 | 0.2278 | 0.6799 | 0.073* | |
C5 | 0.4402 (3) | 0.4198 (2) | 0.68004 (8) | 0.0527 (6) | |
C6 | 0.5907 (3) | 0.4565 (2) | 0.69696 (8) | 0.0532 (6) | |
H6A | 0.6594 | 0.4481 | 0.6723 | 0.064* | |
C7 | 0.5959 (3) | 0.5892 (2) | 0.71400 (7) | 0.0574 (6) | |
H7A | 0.6899 | 0.6063 | 0.7267 | 0.069* | |
H7B | 0.5240 | 0.6007 | 0.7371 | 0.069* | |
C8 | 0.5666 (3) | 0.6791 (2) | 0.67539 (7) | 0.0516 (6) | |
H8A | 0.5361 | 0.7588 | 0.6883 | 0.062* | |
C9 | 0.4467 (3) | 0.6345 (2) | 0.64463 (7) | 0.0507 (5) | |
C10 | 0.3898 (3) | 0.5190 (2) | 0.64651 (8) | 0.0514 (6) | |
C11 | 0.4104 (3) | 0.7329 (3) | 0.61009 (8) | 0.0585 (6) | |
H11A | 0.3727 | 0.8063 | 0.6250 | 0.070* | |
H11B | 0.3362 | 0.7012 | 0.5904 | 0.070* | |
C12 | 0.5432 (3) | 0.7699 (3) | 0.58233 (8) | 0.0586 (6) | |
H12A | 0.5173 | 0.8380 | 0.5626 | 0.070* | |
H12B | 0.5715 | 0.6996 | 0.5639 | 0.070* | |
C13 | 0.6728 (3) | 0.8100 (2) | 0.61110 (8) | 0.0517 (6) | |
C14 | 0.6972 (3) | 0.7048 (2) | 0.64575 (7) | 0.0513 (6) | |
H14A | 0.7129 | 0.6285 | 0.6285 | 0.062* | |
C15 | 0.8427 (3) | 0.7366 (3) | 0.66716 (8) | 0.0632 (7) | |
H15A | 0.8891 | 0.6625 | 0.6789 | 0.076* | |
H15B | 0.8314 | 0.7970 | 0.6910 | 0.076* | |
C16 | 0.9295 (3) | 0.7920 (3) | 0.62790 (9) | 0.0659 (7) | |
H16A | 1.0063 | 0.7356 | 0.6193 | 0.079* | |
H16B | 0.9718 | 0.8712 | 0.6365 | 0.079* | |
C17 | 0.8231 (3) | 0.8106 (3) | 0.58856 (8) | 0.0551 (6) | |
H17A | 0.8285 | 0.7350 | 0.5703 | 0.066* | |
C18 | 0.6419 (3) | 0.9375 (3) | 0.63309 (10) | 0.0661 (7) | |
H18A | 0.5566 | 0.9315 | 0.6511 | 0.099* | |
H18B | 0.6279 | 0.9994 | 0.6104 | 0.099* | |
H18C | 0.7220 | 0.9610 | 0.6515 | 0.099* | |
C19 | 0.3317 (3) | 0.4091 (3) | 0.71907 (8) | 0.0590 (6) | |
H19A | 0.3584 | 0.3405 | 0.7379 | 0.089* | |
H19B | 0.2367 | 0.3953 | 0.7074 | 0.089* | |
H19C | 0.3326 | 0.4849 | 0.7361 | 0.089* | |
C20 | 0.8656 (3) | 0.9204 (3) | 0.55802 (9) | 0.0666 (7) | |
H20Z | 0.8580 | 0.9974 | 0.5755 | 0.080* | |
C21 | 0.7641 (4) | 0.9322 (5) | 0.51798 (12) | 0.1005 (13) | |
H21A | 0.6682 | 0.9494 | 0.5283 | 0.151* | |
H21B | 0.7643 | 0.8555 | 0.5014 | 0.151* | |
H21C | 0.7960 | 0.9990 | 0.4991 | 0.151* | |
C22 | 1.0228 (4) | 0.9080 (3) | 0.54214 (11) | 0.0741 (8) | |
H22A | 1.0846 | 0.9012 | 0.5681 | 0.089* | |
H22B | 1.0321 | 0.8311 | 0.5253 | 0.089* | |
C23 | 1.0756 (4) | 1.0143 (4) | 0.51364 (15) | 0.0984 (12) | |
H23A | 1.0590 | 1.0918 | 0.5295 | 0.118* | |
H23B | 1.0186 | 1.0168 | 0.4866 | 0.118* | |
C24 | 1.2325 (4) | 1.0079 (4) | 0.50092 (13) | 0.0883 (10) | |
H24A | 1.2587 | 0.9211 | 0.4969 | 0.106* | 0.733 (10) |
H24B | 1.2893 | 1.0402 | 0.5255 | 0.106* | 0.733 (10) |
H24C | 1.2431 | 0.9432 | 0.4786 | 0.106* | 0.267 (10) |
H24D | 1.2862 | 0.9814 | 0.5270 | 0.106* | 0.267 (10) |
C251 | 1.2727 (7) | 1.0799 (5) | 0.4585 (3) | 0.088 (2) | 0.733 (10) |
H25A | 1.2127 | 1.0454 | 0.4346 | 0.105* | 0.733 (10) |
C261 | 1.2338 (10) | 1.2166 (6) | 0.4617 (3) | 0.116 (3) | 0.733 (10) |
H26A | 1.1314 | 1.2249 | 0.4651 | 0.175* | 0.733 (10) |
H26B | 1.2640 | 1.2587 | 0.4351 | 0.175* | 0.733 (10) |
H26C | 1.2812 | 1.2528 | 0.4870 | 0.175* | 0.733 (10) |
C271 | 1.4250 (7) | 1.0578 (8) | 0.4448 (3) | 0.127 (3) | 0.733 (10) |
H27A | 1.4479 | 0.9711 | 0.4483 | 0.190* | 0.733 (10) |
H27B | 1.4881 | 1.1070 | 0.4631 | 0.190* | 0.733 (10) |
H27C | 1.4372 | 1.0812 | 0.4141 | 0.190* | 0.733 (10) |
C252 | 1.3037 (13) | 1.1263 (15) | 0.4829 (5) | 0.076 (4) | 0.267 (10) |
H25B | 1.2828 | 1.1972 | 0.5025 | 0.092* | 0.267 (10) |
C262 | 1.233 (4) | 1.145 (4) | 0.4374 (8) | 0.192 (14) | 0.267 (10) |
H26D | 1.1358 | 1.1140 | 0.4383 | 0.288* | 0.267 (10) |
H26E | 1.2863 | 1.1010 | 0.4151 | 0.288* | 0.267 (10) |
H26F | 1.2312 | 1.2325 | 0.4303 | 0.288* | 0.267 (10) |
C272 | 1.4604 (18) | 1.109 (3) | 0.4784 (16) | 0.204 (14) | 0.267 (10) |
H27D | 1.5024 | 1.0978 | 0.5073 | 0.306* | 0.267 (10) |
H27E | 1.5016 | 1.1820 | 0.4646 | 0.306* | 0.267 (10) |
H27F | 1.4795 | 1.0375 | 0.4602 | 0.306* | 0.267 (10) |
O28 | 0.2039 (2) | 0.22733 (18) | 0.65042 (8) | 0.0734 (6) | |
C29 | 0.1753 (4) | 0.1143 (3) | 0.66520 (13) | 0.0832 (10) | |
O301 | 0.2663 (9) | 0.0327 (8) | 0.6663 (4) | 0.095 (3) | 0.62 (4) |
O302 | 0.228 (4) | 0.0265 (18) | 0.6439 (17) | 0.186 (12) | 0.38 (4) |
C31 | 0.0398 (4) | 0.1098 (4) | 0.69085 (16) | 0.1018 (12) | |
H31A | 0.0254 | 0.0269 | 0.7022 | 0.153* | |
H31B | −0.0392 | 0.1320 | 0.6718 | 0.153* | |
H31C | 0.0451 | 0.1674 | 0.7153 | 0.153* | |
O32 | 0.63096 (19) | 0.36908 (19) | 0.73216 (5) | 0.0608 (5) | |
C33 | 0.7731 (3) | 0.3523 (3) | 0.73874 (9) | 0.0630 (7) | |
O34 | 0.8643 (2) | 0.4020 (3) | 0.71683 (8) | 0.0900 (8) | |
C35 | 0.8011 (3) | 0.2691 (3) | 0.77742 (10) | 0.0759 (8) | |
H35A | 0.9028 | 0.2546 | 0.7800 | 0.114* | |
H35B | 0.7524 | 0.1911 | 0.7730 | 0.114* | |
H35C | 0.7662 | 0.3079 | 0.8042 | 0.114* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0599 (16) | 0.0645 (16) | 0.0680 (16) | −0.0031 (14) | −0.0182 (13) | 0.0092 (13) |
C2 | 0.0761 (18) | 0.0797 (19) | 0.0621 (14) | −0.0114 (17) | −0.0165 (15) | −0.0051 (15) |
C3 | 0.0641 (16) | 0.0630 (16) | 0.0680 (15) | −0.0010 (14) | −0.0006 (13) | −0.0091 (13) |
C4 | 0.0592 (15) | 0.0591 (15) | 0.0635 (14) | 0.0069 (13) | 0.0008 (13) | 0.0015 (12) |
C5 | 0.0540 (13) | 0.0563 (13) | 0.0478 (11) | 0.0030 (12) | −0.0023 (11) | 0.0047 (11) |
C6 | 0.0536 (13) | 0.0625 (14) | 0.0436 (11) | 0.0021 (12) | −0.0039 (11) | 0.0126 (11) |
C7 | 0.0614 (14) | 0.0685 (15) | 0.0423 (10) | −0.0083 (13) | −0.0085 (11) | 0.0050 (11) |
C8 | 0.0563 (14) | 0.0524 (13) | 0.0462 (11) | −0.0029 (12) | −0.0032 (11) | 0.0014 (10) |
C9 | 0.0485 (12) | 0.0577 (13) | 0.0460 (11) | 0.0033 (12) | −0.0038 (10) | 0.0042 (11) |
C10 | 0.0481 (12) | 0.0595 (13) | 0.0466 (11) | 0.0009 (12) | −0.0067 (10) | 0.0054 (11) |
C11 | 0.0557 (14) | 0.0617 (14) | 0.0580 (13) | 0.0024 (13) | −0.0094 (12) | 0.0116 (12) |
C12 | 0.0628 (15) | 0.0628 (15) | 0.0503 (12) | 0.0024 (13) | −0.0088 (11) | 0.0135 (12) |
C13 | 0.0532 (13) | 0.0533 (13) | 0.0487 (11) | 0.0003 (11) | 0.0001 (11) | 0.0031 (11) |
C14 | 0.0545 (13) | 0.0561 (13) | 0.0431 (11) | −0.0013 (12) | −0.0045 (10) | 0.0027 (10) |
C15 | 0.0590 (15) | 0.0795 (18) | 0.0512 (12) | −0.0108 (15) | −0.0083 (11) | 0.0059 (13) |
C16 | 0.0588 (15) | 0.0781 (18) | 0.0608 (14) | −0.0087 (15) | −0.0020 (12) | 0.0067 (14) |
C17 | 0.0582 (14) | 0.0583 (14) | 0.0487 (11) | −0.0006 (12) | 0.0014 (11) | 0.0027 (11) |
C18 | 0.0716 (17) | 0.0560 (14) | 0.0709 (15) | 0.0020 (14) | 0.0103 (15) | −0.0015 (13) |
C19 | 0.0593 (15) | 0.0602 (15) | 0.0576 (13) | 0.0002 (12) | 0.0054 (12) | 0.0065 (13) |
C20 | 0.0692 (17) | 0.0693 (16) | 0.0614 (14) | −0.0007 (15) | 0.0067 (14) | 0.0113 (13) |
C21 | 0.086 (2) | 0.133 (3) | 0.083 (2) | −0.017 (2) | −0.0076 (19) | 0.054 (2) |
C22 | 0.0759 (19) | 0.0755 (19) | 0.0708 (16) | 0.0012 (16) | 0.0130 (15) | 0.0091 (16) |
C23 | 0.085 (2) | 0.093 (3) | 0.116 (3) | 0.004 (2) | 0.036 (2) | 0.030 (2) |
C24 | 0.077 (2) | 0.093 (2) | 0.095 (2) | −0.0035 (19) | 0.0192 (18) | 0.014 (2) |
C251 | 0.081 (3) | 0.089 (4) | 0.094 (4) | −0.031 (3) | 0.022 (3) | −0.009 (3) |
C261 | 0.131 (6) | 0.089 (4) | 0.129 (6) | −0.019 (4) | 0.030 (5) | 0.025 (4) |
C271 | 0.085 (4) | 0.140 (6) | 0.156 (7) | −0.028 (4) | 0.051 (5) | −0.004 (5) |
C252 | 0.073 (7) | 0.076 (8) | 0.080 (8) | −0.024 (7) | −0.001 (7) | −0.014 (7) |
C262 | 0.21 (3) | 0.23 (3) | 0.14 (2) | −0.06 (3) | 0.01 (2) | 0.07 (2) |
C272 | 0.094 (13) | 0.19 (3) | 0.32 (4) | −0.067 (16) | 0.03 (2) | 0.03 (3) |
O28 | 0.0671 (12) | 0.0578 (11) | 0.0954 (14) | −0.0046 (10) | 0.0088 (11) | −0.0056 (11) |
C29 | 0.082 (2) | 0.0616 (18) | 0.107 (2) | −0.0112 (18) | 0.0187 (19) | −0.0178 (18) |
O301 | 0.096 (4) | 0.056 (4) | 0.132 (6) | 0.021 (3) | 0.031 (4) | 0.009 (3) |
O302 | 0.22 (2) | 0.100 (8) | 0.24 (3) | −0.058 (10) | 0.132 (19) | −0.068 (12) |
C31 | 0.091 (2) | 0.079 (2) | 0.135 (3) | −0.015 (2) | 0.029 (2) | −0.012 (2) |
O32 | 0.0512 (9) | 0.0758 (12) | 0.0553 (9) | 0.0015 (9) | −0.0064 (8) | 0.0217 (9) |
C33 | 0.0545 (15) | 0.0722 (17) | 0.0622 (14) | 0.0075 (14) | −0.0023 (13) | 0.0093 (14) |
O34 | 0.0587 (11) | 0.1137 (19) | 0.0976 (15) | 0.0029 (12) | 0.0072 (11) | 0.0390 (15) |
C35 | 0.0668 (17) | 0.087 (2) | 0.0740 (16) | 0.0147 (17) | −0.0089 (15) | 0.0185 (16) |
C1—C10 | 1.516 (4) | C19—H19C | 0.9600 |
C1—C2 | 1.521 (4) | C20—C21 | 1.532 (5) |
C1—H1A | 0.9700 | C20—C22 | 1.541 (4) |
C1—H1B | 0.9700 | C20—H20Z | 0.9800 |
C2—C3 | 1.516 (4) | C21—H21A | 0.9600 |
C2—H2A | 0.9700 | C21—H21B | 0.9600 |
C2—H2B | 0.9700 | C21—H21C | 0.9600 |
C3—O28 | 1.456 (3) | C22—C23 | 1.507 (4) |
C3—C4 | 1.513 (4) | C22—H22A | 0.9700 |
C3—H3A | 0.9800 | C22—H22B | 0.9700 |
C4—C5 | 1.554 (4) | C23—C24 | 1.507 (5) |
C4—H4A | 0.9700 | C23—H23A | 0.9700 |
C4—H4B | 0.9700 | C23—H23B | 0.9700 |
C5—C10 | 1.537 (3) | C24—C251 | 1.534 (7) |
C5—C6 | 1.538 (4) | C24—C252 | 1.530 (14) |
C5—C19 | 1.548 (3) | C24—H24A | 0.9700 |
C6—O32 | 1.460 (3) | C24—H24B | 0.9700 |
C6—C7 | 1.513 (4) | C24—H24C | 0.9700 |
C6—H6A | 0.9800 | C24—H24D | 0.9699 |
C7—C8 | 1.530 (3) | C251—C261 | 1.512 (8) |
C7—H7A | 0.9700 | C251—C271 | 1.492 (8) |
C7—H7B | 0.9700 | C251—H25A | 0.9800 |
C8—C9 | 1.523 (3) | C261—H26A | 0.9600 |
C8—C14 | 1.528 (3) | C261—H26B | 0.9600 |
C8—H8A | 0.9800 | C261—H26C | 0.9600 |
C9—C10 | 1.347 (4) | C271—H27A | 0.9600 |
C9—C11 | 1.516 (3) | C271—H27B | 0.9600 |
C11—C12 | 1.539 (4) | C271—H27C | 0.9600 |
C11—H11A | 0.9700 | C252—C262 | 1.529 (17) |
C11—H11B | 0.9700 | C252—C272 | 1.473 (17) |
C12—C13 | 1.542 (4) | C252—H25B | 0.9800 |
C12—H12A | 0.9700 | C262—H26D | 0.9600 |
C12—H12B | 0.9700 | C262—H26E | 0.9600 |
C13—C18 | 1.545 (4) | C262—H26F | 0.9600 |
C13—C14 | 1.550 (3) | C272—H27D | 0.9600 |
C13—C17 | 1.550 (3) | C272—H27E | 0.9600 |
C14—C15 | 1.535 (3) | C272—H27F | 0.9600 |
C14—H14A | 0.9800 | O28—C29 | 1.317 (4) |
C15—C16 | 1.545 (4) | C29—O301 | 1.216 (7) |
C15—H15A | 0.9700 | C29—O302 | 1.238 (17) |
C15—H15B | 0.9700 | C29—C31 | 1.475 (5) |
C16—C17 | 1.551 (4) | C31—H31A | 0.9600 |
C16—H16A | 0.9700 | C31—H31B | 0.9600 |
C16—H16B | 0.9700 | C31—H31C | 0.9600 |
C17—C20 | 1.543 (4) | O32—C33 | 1.346 (3) |
C17—H17A | 0.9800 | C33—O34 | 1.197 (3) |
C18—H18A | 0.9600 | C33—C35 | 1.486 (4) |
C18—H18B | 0.9600 | C35—H35A | 0.9600 |
C18—H18C | 0.9600 | C35—H35B | 0.9600 |
C19—H19A | 0.9600 | C35—H35C | 0.9600 |
C19—H19B | 0.9600 | ||
C10—C1—C2 | 112.4 (2) | C16—C17—H17A | 106.6 |
C10—C1—H1A | 109.1 | C13—C18—H18A | 109.5 |
C2—C1—H1A | 109.1 | C13—C18—H18B | 109.5 |
C10—C1—H1B | 109.1 | H18A—C18—H18B | 109.5 |
C2—C1—H1B | 109.1 | C13—C18—H18C | 109.5 |
H1A—C1—H1B | 107.8 | H18A—C18—H18C | 109.5 |
C3—C2—C1 | 111.3 (2) | H18B—C18—H18C | 109.5 |
C3—C2—H2A | 109.4 | C5—C19—H19A | 109.5 |
C1—C2—H2A | 109.4 | C5—C19—H19B | 109.5 |
C3—C2—H2B | 109.4 | H19A—C19—H19B | 109.5 |
C1—C2—H2B | 109.4 | C5—C19—H19C | 109.5 |
H2A—C2—H2B | 108.0 | H19A—C19—H19C | 109.5 |
O28—C3—C4 | 111.0 (2) | H19B—C19—H19C | 109.5 |
O28—C3—C2 | 106.0 (2) | C21—C20—C22 | 110.3 (3) |
C4—C3—C2 | 110.8 (2) | C21—C20—C17 | 111.8 (3) |
O28—C3—H3A | 109.6 | C22—C20—C17 | 111.1 (2) |
C4—C3—H3A | 109.6 | C21—C20—H20Z | 107.8 |
C2—C3—H3A | 109.6 | C22—C20—H20Z | 107.8 |
C3—C4—C5 | 117.0 (2) | C17—C20—H20Z | 107.8 |
C3—C4—H4A | 108.1 | C20—C21—H21A | 109.5 |
C5—C4—H4A | 108.1 | C20—C21—H21B | 109.5 |
C3—C4—H4B | 108.1 | H21A—C21—H21B | 109.5 |
C5—C4—H4B | 108.1 | C20—C21—H21C | 109.5 |
H4A—C4—H4B | 107.3 | H21A—C21—H21C | 109.5 |
C10—C5—C6 | 108.4 (2) | H21B—C21—H21C | 109.5 |
C10—C5—C19 | 110.4 (2) | C23—C22—C20 | 114.7 (3) |
C6—C5—C19 | 111.16 (19) | C23—C22—H22A | 108.6 |
C10—C5—C4 | 110.67 (19) | C20—C22—H22A | 108.6 |
C6—C5—C4 | 106.7 (2) | C23—C22—H22B | 108.6 |
C19—C5—C4 | 109.5 (2) | C20—C22—H22B | 108.6 |
O32—C6—C7 | 110.59 (19) | H22A—C22—H22B | 107.6 |
O32—C6—C5 | 107.9 (2) | C22—C23—C24 | 115.1 (3) |
C7—C6—C5 | 112.4 (2) | C22—C23—H23A | 108.5 |
O32—C6—H6A | 108.6 | C24—C23—H23A | 108.5 |
C7—C6—H6A | 108.6 | C22—C23—H23B | 108.5 |
C5—C6—H6A | 108.6 | C24—C23—H23B | 108.5 |
C6—C7—C8 | 109.34 (18) | H23A—C23—H23B | 107.5 |
C6—C7—H7A | 109.8 | C23—C24—C251 | 115.0 (4) |
C8—C7—H7A | 109.8 | C23—C24—C252 | 118.0 (6) |
C6—C7—H7B | 109.8 | C23—C24—H24A | 108.5 |
C8—C7—H7B | 109.8 | C23—C24—H24B | 108.5 |
H7A—C7—H7B | 108.3 | C23—C24—H24C | 107.8 |
C9—C8—C14 | 106.51 (18) | C23—C24—H24D | 107.8 |
C9—C8—C7 | 113.0 (2) | C251—C24—H24A | 108.5 |
C14—C8—C7 | 114.4 (2) | C251—C24—H24B | 108.5 |
C9—C8—H8A | 107.6 | C252—C24—H24C | 107.8 |
C14—C8—H8A | 107.6 | C252—C24—H24D | 107.8 |
C7—C8—H8A | 107.6 | H24A—C24—H24B | 107.5 |
C10—C9—C11 | 125.5 (2) | H24C—C24—H24D | 107.1 |
C10—C9—C8 | 123.4 (2) | C261—C251—C271 | 113.5 (6) |
C11—C9—C8 | 111.0 (2) | C261—C251—C24 | 112.1 (6) |
C9—C10—C1 | 123.4 (2) | C271—C251—C24 | 112.3 (6) |
C9—C10—C5 | 123.0 (2) | C261—C251—H25A | 106.1 |
C1—C10—C5 | 113.6 (2) | C271—C251—H25A | 106.1 |
C9—C11—C12 | 111.7 (2) | C24—C251—H25A | 106.1 |
C9—C11—H11A | 109.3 | C262—C252—C272 | 111.1 (19) |
C12—C11—H11A | 109.3 | C262—C252—C24 | 103.8 (18) |
C9—C11—H11B | 109.3 | C272—C252—C24 | 111.0 (15) |
C12—C11—H11B | 109.3 | C262—C252—H25B | 110.3 |
H11A—C11—H11B | 107.9 | C272—C252—H25B | 110.3 |
C11—C12—C13 | 113.2 (2) | C24—C252—H25B | 110.3 |
C11—C12—H12A | 108.9 | C252—C262—H26D | 109.5 |
C13—C12—H12A | 108.9 | C252—C262—H26E | 109.5 |
C11—C12—H12B | 108.9 | C252—C262—H26F | 109.5 |
C13—C12—H12B | 108.9 | H26D—C262—H26E | 109.5 |
H12A—C12—H12B | 107.7 | H26D—C262—H26F | 109.5 |
C12—C13—C18 | 109.9 (2) | H26E—C262—H26F | 109.5 |
C12—C13—C14 | 106.6 (2) | C252—C272—H27D | 109.5 |
C18—C13—C14 | 112.64 (19) | C252—C272—H27E | 109.5 |
C12—C13—C17 | 117.36 (19) | C252—C272—H27F | 109.5 |
C18—C13—C17 | 110.5 (2) | H27D—C272—H27E | 109.5 |
C14—C13—C17 | 99.4 (2) | H27D—C272—H27F | 109.5 |
C8—C14—C15 | 119.70 (18) | H27E—C272—H27F | 109.5 |
C8—C14—C13 | 113.9 (2) | C29—O28—C3 | 120.2 (3) |
C15—C14—C13 | 104.3 (2) | O301—C29—O28 | 122.1 (5) |
C8—C14—H14A | 106.0 | O302—C29—O28 | 116.5 (14) |
C15—C14—H14A | 106.0 | O301—C29—C31 | 123.7 (5) |
C13—C14—H14A | 106.0 | O302—C29—C31 | 125.5 (10) |
C14—C15—C16 | 103.04 (19) | O28—C29—C31 | 112.2 (3) |
C14—C15—H15A | 111.2 | C29—C31—H31A | 109.5 |
C16—C15—H15A | 111.2 | C29—C31—H31B | 109.5 |
C14—C15—H15B | 111.2 | H31A—C31—H31B | 109.5 |
C16—C15—H15B | 111.2 | C29—C31—H31C | 109.5 |
H15A—C15—H15B | 109.1 | H31A—C31—H31C | 109.5 |
C15—C16—C17 | 107.3 (2) | H31B—C31—H31C | 109.5 |
C15—C16—H16A | 110.3 | C33—O32—C6 | 116.3 (2) |
C17—C16—H16A | 110.3 | O34—C33—O32 | 123.6 (3) |
C15—C16—H16B | 110.3 | O34—C33—C35 | 124.9 (3) |
C17—C16—H16B | 110.3 | O32—C33—C35 | 111.5 (2) |
H16A—C16—H16B | 108.5 | C33—C35—H35A | 109.5 |
C20—C17—C13 | 119.5 (2) | C33—C35—H35B | 109.5 |
C20—C17—C16 | 112.7 (2) | H35A—C35—H35B | 109.5 |
C13—C17—C16 | 103.94 (19) | C33—C35—H35C | 109.5 |
C20—C17—H17A | 106.6 | H35A—C35—H35C | 109.5 |
C13—C17—H17A | 106.6 | H35B—C35—H35C | 109.5 |
C10—C1—C2—C3 | 57.8 (3) | C12—C13—C14—C8 | −58.3 (3) |
C1—C2—C3—O28 | 66.2 (3) | C18—C13—C14—C8 | 62.3 (3) |
C1—C2—C3—C4 | −54.4 (3) | C17—C13—C14—C8 | 179.29 (19) |
O28—C3—C4—C5 | −68.0 (3) | C12—C13—C14—C15 | 169.4 (2) |
C2—C3—C4—C5 | 49.5 (3) | C18—C13—C14—C15 | −70.0 (3) |
C3—C4—C5—C10 | −44.6 (3) | C17—C13—C14—C15 | 47.0 (2) |
C3—C4—C5—C6 | −162.4 (2) | C8—C14—C15—C16 | −164.2 (2) |
C3—C4—C5—C19 | 77.2 (3) | C13—C14—C15—C16 | −35.3 (3) |
C10—C5—C6—O32 | 174.13 (19) | C14—C15—C16—C17 | 9.6 (3) |
C19—C5—C6—O32 | 52.7 (3) | C12—C13—C17—C20 | 79.2 (3) |
C4—C5—C6—O32 | −66.6 (2) | C18—C13—C17—C20 | −47.9 (3) |
C10—C5—C6—C7 | 51.9 (2) | C14—C13—C17—C20 | −166.5 (2) |
C19—C5—C6—C7 | −69.5 (3) | C12—C13—C17—C16 | −154.1 (2) |
C4—C5—C6—C7 | 171.17 (19) | C18—C13—C17—C16 | 78.8 (3) |
O32—C6—C7—C8 | 174.9 (2) | C14—C13—C17—C16 | −39.8 (2) |
C5—C6—C7—C8 | −64.5 (3) | C15—C16—C17—C20 | 150.2 (3) |
C6—C7—C8—C9 | 41.3 (3) | C15—C16—C17—C13 | 19.4 (3) |
C6—C7—C8—C14 | −80.8 (3) | C13—C17—C20—C21 | −60.8 (3) |
C14—C8—C9—C10 | 115.5 (3) | C16—C17—C20—C21 | 176.7 (3) |
C7—C8—C9—C10 | −10.9 (3) | C13—C17—C20—C22 | 175.5 (2) |
C14—C8—C9—C11 | −60.0 (3) | C16—C17—C20—C22 | 53.0 (3) |
C7—C8—C9—C11 | 173.6 (2) | C21—C20—C22—C23 | 58.0 (4) |
C11—C9—C10—C1 | −7.3 (4) | C17—C20—C22—C23 | −177.5 (3) |
C8—C9—C10—C1 | 177.8 (2) | C20—C22—C23—C24 | 175.5 (3) |
C11—C9—C10—C5 | 174.8 (2) | C22—C23—C24—C252 | −164.3 (8) |
C8—C9—C10—C5 | 0.0 (4) | C22—C23—C24—C251 | 156.2 (4) |
C2—C1—C10—C9 | 128.1 (3) | C23—C24—C251—C261 | 57.6 (8) |
C2—C1—C10—C5 | −53.8 (3) | C252—C24—C251—C261 | −46.2 (10) |
C6—C5—C10—C9 | −19.8 (3) | C23—C24—C251—C271 | −173.3 (5) |
C19—C5—C10—C9 | 102.2 (3) | C252—C24—C251—C271 | 82.9 (11) |
C4—C5—C10—C9 | −136.5 (3) | C23—C24—C252—C272 | 172 (2) |
C6—C5—C10—C1 | 162.2 (2) | C251—C24—C252—C272 | −94 (2) |
C19—C5—C10—C1 | −75.9 (3) | C23—C24—C252—C262 | −69 (2) |
C4—C5—C10—C1 | 45.5 (3) | C251—C24—C252—C262 | 25.6 (19) |
C10—C9—C11—C12 | −118.3 (3) | C4—C3—O28—C29 | −91.3 (3) |
C8—C9—C11—C12 | 57.1 (3) | C2—C3—O28—C29 | 148.3 (3) |
C9—C11—C12—C13 | −53.6 (3) | C3—O28—C29—O301 | 13.5 (9) |
C11—C12—C13—C18 | −70.6 (3) | C3—O28—C29—O302 | −28 (3) |
C11—C12—C13—C14 | 51.7 (3) | C3—O28—C29—C31 | 177.6 (3) |
C11—C12—C13—C17 | 162.0 (2) | C7—C6—O32—C33 | −82.4 (3) |
C9—C8—C14—C15 | −172.7 (2) | C5—C6—O32—C33 | 154.3 (2) |
C7—C8—C14—C15 | −47.2 (3) | C6—O32—C33—O34 | −2.0 (4) |
C9—C8—C14—C13 | 62.9 (3) | C6—O32—C33—C35 | 175.8 (2) |
C7—C8—C14—C13 | −171.6 (2) |
Experimental details
Crystal data | |
Chemical formula | C31H50O4 |
Mr | 486.71 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 298 |
a, b, c (Å) | 9.2846 (15), 10.7203 (18), 29.982 (4) |
V (Å3) | 2984.2 (8) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.6 × 0.5 × 0.5 |
Data collection | |
Diffractometer | Siemens P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4350, 3393, 2827 |
Rint | 0.043 |
(sin θ/λ)max (Å−1) | 0.622 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.136, 1.05 |
No. of reflections | 3393 |
No. of parameters | 364 |
No. of restraints | 57 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.14, −0.13 |
Computer programs: XSCANS (Siemens, 1996), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
Acknowledgements
We thank VIEP–BUAP for financial support.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The Westphalen rearrangement is a useful synthetic tool in steroid chemistry, involving, for example, a 10β to 5β methyl shift, which has been used for the preparation of Δ9 steroids and 19-nor steroidal derivatives. It was originally applied in the cholestane series, and was further expanded, for instance, to 20-ketopregnanes (Rodig et al., 1961), and more recently, to androstane (Knights & Hanson, 2004) and pregnane series (Pinto et al., 2008, 2009). The mechanism of the rearrangement has been studied (Kočovský & Černý, 1977; Kočovský et al., 1979), although it is not fully understood in a general case, because complex competing reaction pathways are in action (for a review on these mechanisms, see section 2 in Kamernitskii et al., 1987, and references cited therein). A consensus has been reached, however, for products prepared under the Westphalen conditions in the cholestane series. Treatment with acetic anhydride and sulfuric acid promotes dehydration of the cholestan-5α-ol substrate, and the resulting carbocation is rearranged through the methyl 1,2-shift, before formation of the olefinic bond Δ9. The empty p orbital of the carbocation is electronically stabilized by the electron density of the O atom of the acetate at C6. With such a mechanism, a single epimer is expected as product, with the methyl at C5 oriented towards the β face. This stereochemistry has been confirmed in all the studied cases, but, surprisingly, the product of the very first report by Westphalen (1915) was never X-ray characterized.
During a study on the optimization of reaction conditions for the Westphalen rearrangement carried out on 5-hydroxy-5α-cholestane-3β,6β-diyl diacetate, which was the substrate used by Westphalen, we obtained in 80% yield the rearrangement product (see Experimental). The molecular structure (Fig. 1) and the absolute configuration for chiral centers are as expected. The saturated A and C rings have a chair conformation, while the B ring, which includes the C9═C10 double bond, is distorted to a half-chair conformation, close to an envelope with C6 as flap. Finally, the D ring adopts a half-chair conformation twisted on C13—C14. The observed conformation is indeed very similar to that described by Pinto et al. (2008) for the closely related derivative 3β-acetoxy-6β-hydroxy-5β-methyl-19-norcholest-9(10)-ene. An overlay between the steroidal nucleus of this structure and that of the title molecule gives a r.m.s. deviation limited to 0.156 Å, the largest deviation arising from the side chain. This group presents a degree of flexibility, as reflected by the disorder detected in the title compound for the isopropyl group. The same conformation for the A-D ring system was also observed for a Westphalen product in the pregnane series (Pinto et al., 2009).