Crystal structure of 3β-acetoxy-pregna-5,16-dien-20-one (16 DPA)

Article abstract of DOI:10.1007/s10870-005-9000-5

The title compound, 3β-acetoxy-pregna-5,16-dien-20-one, C ₂₃H₃₂O₃, has been synthesized by acetylation followed by oxidation of diosgenin and its crystal structure has been solved from single crystal X-ray diffraction data. The compound crystallizes into orthorhombic space group P2₁2₁2₁ with unit cell parameters: a = 6.031(4) A, b = 12.481(2) A, c = 27.162(5) A, Z = 4. The crystal structure has been refined to R = 0.0597 for 1291 observed reflections. Rings A and C of the compound are in chair conformation whereas ring B is in half-chair conformation. Ring D is in envelop conformation. The A/B ring junction is quasi-trans, while ring systems B/C and C/D are trans fused about the C8-C9 and C13-C14 bonds, respectively. The steroid nucleus has a small twist, as shown by the C19-C10...C13-C18 pseudo-torsion angle of 9.5°. The crystal packing is determined by a pair of weak C-H...O hydrogen bonds in addition to van der Waals interactions.

Full text of DOI:10.1007/s10870-005-9000-5

ꢀ
C
Journal of Chemical Crystallography, Vol. 36, No. 3, March 2006 ( 2006)
DOI: 10.1007/s10870-005-9000-5
Crystal structure of 3β-acetoxy-pregna-5,16-dien-20-one
(16 DPA)
Pankaj Bandhoria,(1) Vivek K. Gupta,(1)∗ D. K. Gupta,(2) S. M. Jain,(2) and B. Varghese(3)
Received April 2, 2005; accepted May 25, 2005
Published Online January 21, 2006
The title compound, 3β-acetoxy-pregna-5,16-dien-20-one, C23H32O3, has been synthesized
by acetylation followed by oxidation of diosgenin and its crystal structure has been solved
from single crystal X-ray diffraction data. The compound crystallizes into orthorhombic
˚
˚
space group P212121 with unit cell parameters: a = 6.031(4) A, b = 12.481(2) A, c =
˚
27.162(5) A, Z = 4. The crystal structure has been refined to R = 0.0597 for 1291 observed
reflections. Rings A and C of the compound are in chair conformation whereas ring B
is in half-chair conformation. Ring D is in envelop conformation. The A/B ring junction
is quasi-trans, while ring systems B/C and C/D are trans fused about the C8–C9 and
C13–C14 bonds, respectively. The steroid nucleus has a small twist, as shown by the C19–
C10· · ·C13–C18 pseudo-torsion angle of 9.5◦. The crystal packing is determined by a pair
of weak C–H· · ·O hydrogen bonds in addition to van der Waals interactions.
KEY WORDS Crystal structure; steroid; ring conformation; half-chair; envelope torsion angle; direct methods.
Introduction
gies, and various eye diseases, and in cases of
adrenal insufficiency, or the malfunctioning of the
Steroids are a large group of naturally oc-
adrenal cortex. The title compound, a steroid, is
a key intermediate used for making residual hor-
mone medicines such as cortisone, progesterone,
testosterone, floucinoline acetonide etc. The study
being reported in this paper is a part of our on-
going work on the synthesis and structure analysis
of a variety of steroids.1–11
curring and synthetic lipids with a great diver-
sity of physiological activity. Included among the
steroids are many important hormones. Steroid
hormonesincludecortisone, progesterone, andthe
female and male sex hormones (estradiol; testos-
terone). Perhaps the most widely used steroids
in medicine are cortisone and progesterone and
their various synthetic derivatives. These steroids
are prescription drugs used for a variety of skin
ailments, rheumatoid arthritis, asthma and aller-
Experimental
Synthesis of 3β-acetoxy-pregna-5,16-dien-
20-one
(1) Department of Physics, University of Jammu, Jammu Tawi
180 006, India.
(2) Regional Research Laboratory, Jammu Tawi 180 001, India.
(3) Sophisticated Analytical Instrument Facility, Indian Institute of
Technology, Madras, Chennai 600 036, India.
To whom correspondence should be addressed; e-mail:
vivek gupta2k2@hotmail.com
A mixture of diosgenin (1) (4.9 g) and acetic
anhydride (10 mL) was heated at 195◦C at ele-
vated pressure for an hour to give pseudodios-
genin diacetate (2). The resulting solution was
∗
161
ꢀ
C
1074-1542/06/0300-0161/0 2006 Springer Science+Business Media, Inc.

162
Bandhoria, Gupta, Gupta, Jain, and Varghese
Scheme 1.
brought to room temperature and diluted with wa-
ter (1.5 mL) and acetic acid (10 mL). The mixture
was cooled to 10◦C and to this was added a so-
lution of chromic anhydride (2 g) in acetic acid
(10 mL) with stirring maintaining the temperature
between 10–15◦C and the stirring was continued
for 3 h at this temperature. This resulted in the
oxidation of 2 to yield the ester 3. Sodium bisul-
phite (2 g) in water (5 mL) was added to the mix-
ture which was then refluxed for an hour, cooled
and poured in water (200 mL). The precipitated
solid was filtered,washed with water and dried at
room temperature. Repeated crystallization from
methanol gave 3β-acetoxy-pregna-5,16-dien-20-
one (4) as crystals (2.3 g), m.p. 171–2◦C. The
reaction steps are shown in Scheme 1.
dimensional intensity data collection on an Enraf
Nonius CAD-4 diffractometer using MoKα
˚
radiation (λ = 0.71073 A). A total of 2122
reflections were recorded and out of this number
1292 reflections (0 ≤ h ≤ 7, 0 ≤ k ≤ 14, 0 ≤ l ≤
32) were treated as observed. The structure was
solved by direct methods (SHELXS97).12 All
the non-hydrogen atoms of the molecule were
obtained from E-map. Full-matrix least-squares
refinement was carried out using SHELXL97
software.12 Out of 32 H atoms, 26 H atoms were
located directly from a Fourier map and refined
isotropically. The positions of the remaining
H atoms were determined in accordance with
the relevant geometry and refined as a riding
˚
model, with C–H distances 0.96 A and with
Uiso(H) = 1.5Ueq(C). The final refinement cycles
converged to an R = 0.0597 and wR(F2) =
Crystal structure determination and refinement
0.1748
[1/[σ2(Fo2) + (0.1774P)2 + 0.00P ]
A crystal having good morphology (0.3 mm
× 0.2 mm × 0.2 mm) was chosen for three-
where P = [Fo2 + 2Fc2]/3 Maximum shift to
e.s.d. ratio for all atoms in the final cycle is

3β-acetoxy-pregna-5,16-dien-20-one
163
Table 1. Crystal Data and Experimental Details
0.153 (for y H11). Final cycles of refinement
resulted in a residual ele−c3tron density in the
CCDC deposition no.
259203
˚
range −0.243 to 0.244 eA . Atomic scattering
Crystal description
Chemical formula
Molecular weight
Cell parameters
Colourless plate
C
23H32O3
factors were taken from International Tables for
X-ray Crystallography (1992, Vol. C, Tables
4.2.6.8 and 6.1.1.4). The crystallographic data are
summarized in Table 1. CCDC-259203 contains
the supplementary crystallographic data for this
paper.
356.49
˚
a (A)
6.031(4)
˚
b (A)
12.481(2)
27.162(5)
2044.6(14)
Orthorhombic, P212121
1.158
˚
c (A)
3
˚
Unit cell volume (A )
Crystal system, space group
Density (calculated, Mg m−3
)
No. of molecules per unit cell, Z
Radiation, Wavelength A
4
˚
MoKα, 0.71073
776
Results and discussion
F(0 0 0)
θ range for entire data collection 2.22 < θ < 24.96◦
Selected bond distances, bond angles, and
torsion angles are listed in Table 2. An ORTEP
view of the molecule with the atomic numbering
scheme is shown in Fig. 1.13 The geometry of the
molecule has been calculated using the software
WinGX14 and PARST.15,16
Bond distances and bond angles of the title
compound are in good agreement with the cor-
responding values obtained in case of related 5-
ene steroid molecules.3,9,17–21 Mean bond lengths
No. of measured reflections
No. of unique reflections
No. of observed reflections
No. of parameters refined
Refinement method
Final R-factor
2122
2097
1291 [Fo > 4σ (Fo)]
340
Full-matrix least-squares on F2
0.0597
0.1748
1.056
−0.243 < ꢀρ < 0.244
wR(F2)
Goof (S) on F2
Final r−e3sidual electron density
˚
(eA
)
(ꢀ/σ)max in the final cycle
0.153 (for y H11)
3
3
3
2
˚
[C(sp )–C(sp ) = 1.532(9) A; C(sp )–C(sp ) =
2
2
˚
˚
1.499(9) A; C(sp ) = C(sp ) = 1.325(9) A] are
comparable to the theoretical values as reported by
Allen et al.22 The C20–O1, C22–O3 and C16–C17
bond lengths indicate double-bond nature (Ta-
ble 2). The bond angles C13–C14–C8, C17–C13–
C12, C17–C13–C14, C14–C13–C18, C8–C14–
C15, C15–C14–C13 show some significant de-
viation from the ideal tetrahedral value of 109.4◦.
Deviations of this kind are commonly observed
in steroids and this is attributed to the strain in-
duced by fusion of five and six-membered rings
and bond unsaturations.
Fig. 1. ORTEP view of the molecule with displacement ellipsoids drawn at 50%
probability level.

164
Bandhoria, Gupta, Gupta, Jain, and Varghese
◦
◦
˚
Table 2. Selected bond lengths (A), bond angles ( ) and torsion angles ( ) for non hydrogen
atoms (e.s.d.’s are given in parentheses)
˚
Bond lengths (A)
C5–C6
C20–O1
Bond angles (◦)
C8–C14–C15
1.318(9)
1.230(8)
C16–C17
C22–O3
1.332(9)
1.209(9)
122.8(5)
103.6(5)
118.7(5)
−60.2(8)
C8–C14–C13
C14–C13–C18
C17–C13–C14
C2–C3–C4–C5
115.4(4)
113.2(5)
100.0(5)
57.9(8)
C13–C14–C15
C17–C13–C12
C1–C2–C3–C4
Torsion angles (◦)
C2–C1–C10–C5
C4–C5–C10–C1
C6–C7–C8–C9
C7–C8–C9–C10
C8–C9–C11–C12
C9–C11–C12–C13
C10–C5–C6–C7
C12–C13–C14–C8
C14–C8–C9–C11
C14–C13–C17–C16
C17–C13–C14–C15
−47.1(9)
45.5(7)
40.2(7)
−59.1(6)
−50.4(8)
51.5(8)
C3–C4–C5–C10
C5–C6–C7–C8
−53.0(8)
−11.9(9)
−16.3(7)
46.1(6)
−60.7(6)
55.9(10)
−53.6(7)
34.5(6)
C6–C5–C10–C9
C8–C9–C10–C5
C9–C8–C14–C13
C10–C1–C2–C3
C11–C12–C13–C14
C13–C14–C15–C16
C14–C15–C16–C17
C15–C16–C17–C13
−0.5(10)
62.1(6)
51.7(6)
25.4(6)
−36.6(6)
−19.9(7)
−3.5(7)
The overall shape of ring A is very close
C9) = 10.45]. The conformation of ring D is 14α-
envelope [ꢀCs(C14 = 4.16)] with pseudorotation
parameters ꢀ = −25.22 and ϕm = −37.53.27
to the chair conformation typical for totally sat-
urated A rings. However, some distortion from
the ideal form could be expressed as due to the
loss of rotational symmetry, with rotational axis
passing through C1–C2 and C4–C5 bonds
[ꢀC2(C1–C2) = 12.75], with the retention of per-
pendicular mirror symmetry [ꢀCs(C3) = 2.32].
˚
Atom C14 is disposed 0.59 A below the plane
defined by the other four ring atoms.
The C3· · ·C16 distance, which is a measure
˚
of the length of the steroid nucleus, is 8.739 A. The
distance between terminal atoms C21 and C23
˚
˚
In ring B, the C5 = C6 distance of 1.318(9) A
is 14.543 A. The C19–C10· · ·C13–C18 pseudo-
confirms the localization of a double bond at this
position. This double bond imposes an half-chair
conformation on ring B with the rotational axis
bisecting C5–C6 and C8–C9 bonds and with the
asymmetry parameter [ꢀC2(C5–C6) = 5.20].
Similar observations on the conformation of ring
B in related structures21,23–25 have been reported.
Atoms C8 and C9 are displaced to opposite sides
by 0.303(5) and 0.417(6), respectively, from the
mean C10/C5/C6/C7 plane.26
torsion angle, which gives a measure of the molec-
ular twist, is 9.5◦. Newman projections along the
bonds involved in ring fusion are shown in Fig. 2.
Atoms H8 and H9, as well as C18 and H14, have
antiperiplanar configurations.
The conformation of O1 relative to C13
is assigned one of the qualitative descriptors,
syn-periplanar, syn-clinal, anti-clinal, or anti-
periplanar in accordance with the definition of
Klyne and Prelog.28 In the present study, the car-
bonyl oxygen atom O1 is oriented over the D-ring
syn-periplanar to the C13–C17 bond [C13–C17–
C20–O1 = −5.0(9)◦]. The conformation of the
side chain at C17 is further illustrated in Fig. 3.
Packing view of the molecules in the unit
cell viewed down a-axis is shown in Fig. 4. Atom
Nevertheless, the overall shape of the C ring
is still approximately the chair conformation typ-
ical for totally saturated C rings. Ring C, because
of strain at the junction with the five-membered D
ring [C12–C13–C14–C8 torsion angle over 60◦],
has a distorted form [ꢀCs(C8) = 8.60, ꢀC2(C8–

3β-acetoxy-pregna-5,16-dien-20-one
165
Fig. 4. Appearance of chains of molecules that are head-to-
tail hydrogen bonded.
jacent chain links are rotationally related. Chains
of hydrogen-bonded molecules are packed with
van der Waals contacts. In the packing diagram
it can also be seen that the acetate groups lie in
layers perpendicular to the c-axis.
Fig. 2. Newman projections along (a) C5–C10 (b) C8–C9
(c) C13–C14 (angles given in degree).
Supplementary material CCDC-259203 contains the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html
[or from the Cambridge Crystallographic Data Centre(CCDC), 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033;
email: deposit@ccdc.cam.ac.uk].
C23 acts as a donor for a weak intermolecular
C–H· · ·O hydrogen bond with carbonyl atom O1
of an adjacent molecule (see Table 3 for details).
This interaction links the molecules head-to-tail
into chains that run parallel to the c-axis. The ad-
Table 3. Geometry of Intra- and Intermolecular C–H· · ·O Hydrogen
Bonds With e.s.d.’s in parentheses.
D–H
H· · ·A
D· · ·A
D–H· · ·A
D–H· · ·A
(A)
(A)
(A)
(◦)
˚
˚
˚
C12–H121· · ·O1
1.00(7) 2.54(6)
3.09(1)
3.60(1)
114(4)
158(6)
C23–H23B· · ·O1a 0.96(1) 2.69(6)
Fig. 3. Newman projection with torsion angles about the
C17–C20 bond (angles given in degree).
Symmetry code: (a)−x + 3/2, −y + 1, z + 1/2.

166
Bandhoria, Gupta, Gupta, Jain, and Varghese
9. Rajnikant; Gupta, V.K.; Firoz, J.; Shafiullah; Gupta, R. Crystal-
logr. Rep. 2001, 46(3), 415.
Acknowledgments
10. Rajnikant; Gupta, V.K.; Hashmi, S.; Shafiullah; Varghese, B.;
Dinesh. Crystallogr. Rep. 2002, 47(1), 75.
11. Rajnikant; Gupta, V.K.; Khan, E.H.; Shafi, S.; Shafiullah,
Dinesh. J. Chem. Crystallogr. 2002, 32(9), 325.
12. Sheldrick, G.M. SHELXS97; University of Gottingen: Germany,
1997.
13. Farrugia, L.J. J. Appl. Crystallogr. 1997, 30, 565.
14. Farrugia, L.J. J. Appl. Crystallogr. 1999, 32, 837.
15. Nardelli, M. Comput. Chem. 1983, 7, 95.
The authors are thankful to the Head,
SAIF, IIT, Madras, Chennai for the use of the
data collection facility. One of us (Vivek) is
thankful to the University Grants Commission,
Government. of India, for research funding under
DRS Programme [Project No. F-530/1/DRS/2001
(SAP-I)].
16. Nardelli, M. J. Appl. Crystallogr. 1995, 28, 659.
17. Duax, W.L.; Norton, D.A. Atlas of Steroid Structures; Plenum:
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18. Griffin, J.F.; Duax, W.L.; Weeks, C.M. Atlas of Steroid Struc-
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