3,17-Dioxoandrost-4-en-4-yl acetate

Article abstract of DOI:10.1107/S0108270107015533

The title compound, C21H28O4, has a 4-acet-oxy substituent positioned on the steroid face. The six-membered ring A assumes a conformation inter-mediate between 1,2Β-half chair and 1-sofa. A long Csp ³ - Csp ³ bond is observed in ring B and reproduced in quantum-mechanical ab initio calculations of the isolated mol-ecule using a mol-ecular-orbital Hartree-Fock method. Cohesion of the crystal can be attributed to van der Waals inter-actions and weak C - H...O hydrogen bonds. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107015533

organic compounds
Ê
deviating signi®cantly from the average value of 1.535 (14) A.
Acta Crystallographica Section C
Crystal Structure
Communications
The abnormally large value is probably due to the severe
distortion of ring A (C1±C5/C10). A similar C9ÐC10 bond
length was observed for one of the non-equivalent molecules
ISSN 0108-2701
Ê
in the asymmetric unit of formestane [1.571 (3) A; Grif®n et
al., 1980].
3,17-Dioxoandrost-4-en-4-yl acetate
As a consequence of the C4 C5 double bond present in
ring A, this ring assumes a conformation intermediate
between 1ꢀ,2ꢁ-half chair and 1ꢀ-sofa [asymmetry parameters
(Duax & Norton, 1975): ÁC2(1,2) = 12.5 (3)ꢀ, ÁCs(1) =
13.7 (2)ꢀ and ÁCs(3) = 45.1 (2)ꢀ]. Rings B (C5±C10) and C
(C8/C9/C11±C14) have sightly distorted chair conformations,
with average torsion angles of 54.0 (18) and 55 (2)ꢀ, respec-
tively. The ®ve-membered ring D (C13±C17) has a 14ꢀ
conformation, most common for these 17-one steroids
L. C. R. Andrade,a J. A. PaixÄao,a M. J. M. de Almeida,a
F. M. Fernandes Roleirab and E. J. Tavares da Silvab*
aCEMDRX, Department of Physics, University of Coimbra, P-3004-516 Coimbra,
b
Ã
Â
Â
Portugal, and Centro de Estudos Farmaceuticos, Laboratorio de Quõmica
Ã
Farmaceutica, Faculty of Pharmacy, University of Coimbra, P-3000-295 Coimbra,
Portugal
Correspondence e-mail: jap@pollux.fis.uc.pt
[puckering parameters (Cremer & Pople, 1975): q2
=
ꢀ
Ê
0.417 (3) A and '2 = 215.6 (4) ; pseudorotation (Altona et al.,
1968) and asymmetry parameters (Duax & Norton, 1975): Á =
34.4 (4)ꢀ, 'm = 42.7 (1)ꢀ, ÁCs(14) = 0.7 (2)ꢀ, ÁC2(13,14) =
20.0 (2)ꢀ]. The distance between terminal atoms O3 and O17 is
Received 28 March 2007
Accepted 29 March 2007
Online 11 May 2007
The title compound, C21H28O4, has a 4-acetoxy substituent
positioned on the steroid ꢀ face. The six-membered ring A
assumes a conformation intermediate between 1ꢀ,2ꢁ-half
chair and 1ꢀ-sofa. A long Csp3ÐCsp3 bond is observed in ring
B and reproduced in quantum-mechanical ab initio calcula-
tions of the isolated molecule using a molecular-orbital
Hartree±Fock method. Cohesion of the crystal can be
attributed to van der Waals interactions and weak CÐ
HÁ Á ÁO hydrogen bonds.
Ê
10.564 (2) A. The C19ÐC10Á Á ÁC13ÐC18 pseudo-torsion
angle of 0.06 (19)ꢀ indicates that the molecule is not twisted.
The dihedral angle between the least-squares plane of the four
non-H atoms of the acetate group and that of ring A is
79.78 (10)ꢀ.
In order to check whether the observed large deviations
from the mean of the C9ÐC10 and C12ÐC13 bond lengths
were intrinsic to the free steroid molecule or rather due to an
in¯uence of crystal packing, we have performed a quantum
mechanical calculation of the equilibrium geometry of the free
molecule. These calculations were performed with the
computer program GAMESS (Schmidt et al., 1993). A mol-
ecular-orbital Roothan Hartree±Fock method was used with
an extended 6-31G(d,p) basis set. Tight conditions for
convergence of both the self-consistent ®eld cycles and the
Comment
Following our interest in preparing steroidal enzymatic inhi-
bitors aimed at breast cancer treatment and in studying their
structure±activity relationships (Cepa et al., 2005), the title
compound, (I), which is the acetate derivative of formestane,
was prepared as previously described in the literature (Marsh
et al., 1985). We report here the molecular structure of (I)
determined by single-crystal X-ray analysis, and compare it
with that of the free molecule as given by quantum-mechanical
ab initio calculations.
5
maximum density and energy gradients were imposed (10
An ORTEPII (Johnson, 1976) plot of (I) is shown in Fig. 1.
The 4-acetoxy substituent is positioned on the ꢀ face of the
steroid nucleus. Average values for the atomic distances are in
good agreement with reported values (Allen et al., 1987),
although for the Csp3ÐCsp3 bonds, extreme values of
Figure 1
A plot of the title compound. Displacement ellipsoids are drawn at the
50% probability level and H atoms are shown as small spheres of
arbitrary radii.
Ê
1.514 (3) (C12ÐC13) and 1.569 (3) A (C9ÐC10) were found,
o330 # 2007 International Union of Crystallography
DOI: 10.1107/S0108270107015533
Acta Cryst. (2007). C63, o330±o331

organic compounds
Table 1
Selected bond lengths (A).
atomic units). The programs were run on a Pentium IV PC
(3.0 GHz) running Linux. Interestingly, the calculations
Ê
Ê
reproduce the long C9ÐC10 bond (calculated value 1.570 A).
O4ÐC4
C2ÐC3
C3ÐC4
1.409 (3)
1.498 (3)
1.465 (3)
C4ÐC5
C9ÐC10
C12ÐC13
1.334 (3)
1.569 (3)
1.514 (3)
For the shorter Csp3ÐCsp3 bond, the calculations give a
slightly higher value than the observed value (calculated value
Ê
1.526 A). Overall, there is a very good agreement between the
remaining calculated and observed bond lengths. However,
the equilibrium geometry of the isolated molecule has a
signi®cantly more twisted steroid nucleus (calculated pseudo-
torsion angle C19ÐC10Á Á ÁC13ÐC18 = 4.9ꢀ). There is
considerable freedom of rotation of the acetoxy group around
the C4ÐO4 and O4ÐC41 bonds, as evidenced by the torsion
angles C3ÐC4ÐO4ÐC41 [experimental 80.0 (2)ꢀ; calculated
77.0ꢀ] and C4ÐO4ÐC41ÐO41 [experimental 0.4 (4)ꢀ; calcu-
lated 15.4ꢀ].
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
C6ÐH6AÁ Á ÁO4
C6ÐH6BÁ Á ÁO3i
C11ÐH11BÁ Á ÁO41ii
0.97
0.97
0.97
2.34
2.42
2.54
2.808 (3)
3.358 (3)
3.459 (3)
109
164
159
1
Symmetry codes: (i) x; y
;
z ‡ 32; (ii) x ‡ 21; y ‡ 1; z ‡ 12.
2
Owing to the absence of a strong hydrogen-bond donor,
cohesion of the structure of (I) is mainly achieved by van der
Waals and weak CÐHÁ Á ÁO interactions. One intramolecular
CÐHÁ Á ÁO short contact between the single-bonded O atom of
the 4-acetoxy group and a neighbouring H atom of ring B is
All H atoms were re®ned as riding on their parent atoms, with CÐ
Ê
H = 0.96±0.98 A and Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). The
absolute con®guration was not determined from the X-ray data but
was known from the synthesis route. Friedel pairs were merged
before re®nement.
Ê
present [C6ÐH6AÁ Á ÁO4 = 2.808 (5) A]. There are, in addition,
Data collection: CAD-4 Software (Enraf±Nonius, 1989); cell
re®nement: CAD-4 Software; data reduction: PLATON (Spek, 2003);
program(s) used to solve structure: SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: ORTEPII (Johnson, 1976); software used to
prepare material for publication: SHELXL97.
two intermolecular CÐHÁ Á ÁO short distances of 3.357 (6) and
Ê
3.459 (6) A between H atoms of rings B and C and O atoms.
Experimental
To an ice-cooled solution of formestane (0.3 g, 0.99 mmol) in pyridine
(5.0 ml), acetyl chloride (0.11 ml, 1.48 mmol) was added, and the
reaction was stirred for 3 h until completion. Dichloromethane
(100 ml) was then added, and the organic layer was washed with
aqueous 0.25 N HCl (2 Â 100 ml), 10% NaHCO3 (2 Â 100 ml) and
water (2 Â 100 ml), dried over anhydrous MgSO4 and evaporated to
dryness giving the desired title compound as a yellow crystalline solid
(yield 0.335 g, 98%). Crystals of (I) of good quality suitable for X-ray
crystallographic analysis were grown from ethyl acetate [m.p. 457±
458 K; literature m.p. 457.0±457.5 K (Marsh et al., 1985)]. IR (NaCl
salt plate, ꢂ, cm 1): 1758, 1735, 1681, 1625; 1H NMR (CDCl3): ꢃ 0.91
(s, 3H, 18-H3), 1.27 (s, 3H, 19-H3), 2.24 [s, 3H, CH3C(O)O], 2.73 (ddd,
1H, J6ꢀÐ6ꢁ = 15.0 Hz, J6ꢀÐ7ꢀ = 4.0 Hz, J6ꢀÐ7ꢁ = 2.5 Hz, 6ꢀ-H).
Ã
This work was supported by FundacËaÄo para a Ciencia e
Tecnologia under programme No. POCI2010.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3116). Services for accessing these data are
described at the back of the journal.
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3
Ê
C21H28O4
Mr = 344.43
V = 1886.6 (3) A
Z = 4
Orthorhombic, P212121
Ê
Cu Kꢀ radiation
1
a = 11.5681 (3) A
ꢄ = 0.66 mm
T = 294 (2) K
Ê
b = 12.0702 (3) A
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Ê
c = 13.512 (2) A
0.36 Â 0.17 Â 0.17 mm
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Enraf±Nonius MACH-3
diffractometer
Absorption correction: scan
(North et al., 1968)
Tmin = 0.851, Tmax = 0.890
3577 measured re¯ections
2135 independent re¯ections
1795 re¯ections with I > 2ꢅ(I)
Rint = 0.022
3 standard re¯ections
frequency: 300 min
intensity decay: 2.2%
Schmidt, M. W., Baldrige, K. K., Boatz, J. A., Elbert, S. T., Gordon, M. S.,
Jensen, J. J., Koseki, S., Matsunaga, N., Nguyen, K. A., Sue, S., Windus, T. L.,
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Re®nement
R[F2 > 2ꢅ(F2)] = 0.029
wR(F2) = 0.088
S = 1.09
230 parameters
H-atom parameters constrained
3
Ê
Áꢆmax = 0.16 e A
È
Gottingen, Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7±13.
3
Ê
0.15 e A
2128 re¯ections
Áꢆmin
=
ꢁ
Acta Cryst. (2007). C63, o330±o331
Andrade et al. C21H28O4 o331