Synthesis and X-ray crystallographic analysis of 17α-hydroxy-17- methylandrost-4-ene-17-one

Article abstract of DOI:10.1007/s10870-005-9058-0

17α-Hydroxy-17-methylandrost-4-ene-17-one is a complex of two steroid molecules with water and its crystal structure has been determined by X-ray crystallographic techniques. The transparent plate-like crystals of this compound crystallized in the orthorhombic space group P2₁2 ₁2₁, with unit cell parameters: a = 6.382(2), b = 12.841(5), c = 43.350(2) A, λ(Mo Kα) = 0.71073 A, Z = 8. The structure has been solved by direct methods and refined to R = 0.047, wR = 0.086. There are two crystallographically independent molecules, I and II, in the asymmetric unit. In both the molecules, rings A and D adopt a distorted half-chair conformation while rings B and C exist in chair conformation. The crystal structure is stabilized by intermolecular O-H...O and C-H...O hydrogen bonds.

Full text of DOI:10.1007/s10870-005-9058-0

Journal of Chemical Crystallography, Vol. 36, No. 5, May 2006 (ꢀC 2006)
DOI: 10.1007/s10870-005-9058-0
Synthesis and X-ray crystallographic analysis
of 17α-hydroxy-17-methylandrost-4-ene-17-one
(1)∗
(1)
(1)
Rajnikant Verma,
Dinesh Jasrotia, and Mousmi Bhat
Received August 26, 2005; accepted November 4, 2005
Published Online February 14, 2006
17α-Hydroxy-17-methylandrost-4-ene-17-one is a complex of two steroid molecules with
water and its crystal structure has been determined by X-ray crystallographic techniques.
The transparent plate-like crystals of this compound crystallized in the orthorhombic space
˚
group P212121, with unit cell parameters: a = 6.382(2), b = 12.841(5), c = 43.350(2) A,
˚
λ(Mo Kα) = 0.71073 A, Z = 8. The structure has been solved by direct methods and refined
to R = 0.047, wR = 0.086. There are two crystallographically independent molecules, I and
II, in the asymmetric unit. In both the molecules, rings A and D adopt a distorted half-chair
conformation while rings B and C exist in chair conformation. The crystal structure is
stabilized by intermolecular O−H· · ·O and C−H· · ·O hydrogen bonds.
KEY WORDS: X-ray crystallography; crystal structure; ring conformations; hydrogen bonds.
Introduction
Experimental
Selected by the evolutionary process to per-
A solution of 10 g of pregnenolone in a mix-
ture of 50 mL of tetrahydrofuran and 140 mL of
t-butanol containing potassium t-butoxide (from
6.4 g of potassium metal) is oxygenated at 5–
form some of the most fundamental biological
1
,2
functions, the steroid system not only has in-
spired the endocrinologists, but has also become
the basis for some of the most phenomenal devel-
opment in organic chemistry. The substituents at
C3 position of the steroid moiety are either linked
by intra or intermolecular hydrogen bonds that
◦
7 until 1.1 molar equivalents of oxygen have
been consumed. Nitrogen is passed through the
solution for several minutes and the reaction mix-
◦
ture is then heated to 60–70 C for 20 min. Pre-
3
help in understanding the stacking interactions.
cipitation with water and crystallization gives
7.4 g of 3β-hydroxyandrost-5-ene-17-one which
on treatment with methylmagnesium iodide gives
the 17α-methyl compound, which is then oxi-
dized to yield 17α-hydroxy-17-methylandrost-4-
ene-17-one. Solvent loss technique was then em-
ployed for the growth of transparent plate shaped
crystals (mp 434 K) using methanol as the solvent
system.
The study being reported in this paper is a
part of our ongoing work on synthesis, structure
analysis, and role of hydrogen bonding in steroidal
3–10
molecules.
(
1)
Post Graduate Department of Physics, Condensed Matter Physics
Group, University of Jammu, Jammu Tawi 180 006, India.
To whom correspondence should be addressed; e-mail:
rkantverma@rediffmail.com.
∗
Three-dimensional intensity data of a sin-
gle crystal of the title compound were collected
2
83
1
074-1542/06/0500-0283/0 ꢀC 2006 Springer Science+Business Media, Inc.

2
84
Verma, Jasrotia, and Bhat
on an Enraf-Nonius CAD-4 diffractometer using
crystallographically independent molecules (I and
II) were found in the asymmetric unit cell. All
non-hydrogen atoms of both the molecules were
located from the E-map.
˚
MoKα radiation (λ = 0.71073 A) and ω-2θ scan
mode was employed for data collection. The unit
cell parameters were refined from accurately de-
termined 25 reflections in the range (6.16 < θ <
Refinement was carried out by using full-
◦
2
1
0.32 ). A total number of 3681 reflections were
matrix method on F using SHELXL97 soft-
◦
12
recorded in the range 2.12 ≤ θ ≤ 24.95 . From
the number of reflections as recorded, 3602 were
found unique (with index range: 0 ≤ h ≤ 7, 0
ware. Initially, the isotropic refinement of all
the non-hydrogen atoms brought the reliability
index down to 0.156. All hydrogens were fixed
stereochemically. Finally, the R-factor converged
≤
k ≤ 15, 0 ≤ l ≤ 51) and 1537 were treated
2
as observed [F > 4σ(F )]. Two standard reflec-
to 0.047 [wR(F ) = 0.086] after few cycles of
o
o
¯
¯ ¯
tions (2 3 1 and 1 1 3) were monitored every 100
reflections to check for crystal deterioration, if
any, during beam exposure to the sample. The
data were corrected for Lorentz and polarization
effects. Absorption (µ = 0.074 mm ) and ex-
tinction (0.001) corrections were not applied.
The crystal structure has been solved by di-
refinement. The maximum positive and negative
electron density (ꢀρ) in final difference Fourier
–
3
˚
map ranges from 0.13 to −0.13 e A , respec-
2
tively. The goodness-of-fit on F is 0.812. Atomic
−
1
scattering factors were taken from International
Tables for Crystallography (1992, Vol. C, Tables
4.2.6.8 and 6.1.1.4). The crystallographic data are
listed in Table 1.
11
rect methods using SHELXS97 software. Two

1
7α-hydroxy-17-methylandrost-4-ene-17-one
285
Table 1. Crystal Data and Structure Refinement Details
˚
◦
Table 2. Bond Distances (A) and Bond Angles ( ) for Non-
Hydrogen Atoms (ESDs are Given in Parentheses)
Crystal description
CCDC reference no
Chemical formula
Molecular weight
Crystal system
Transparent rectangular plates
CCDC 217672
C20H30O2·H2O
319.46
Orthorhombic
P212121
Molecule I
Molecule II
˚
Bond distances (A)
C1–C2
C1–C10
C2–C3
C3–O1
C3–C4
C4–C5
C5–C6
C5–C10
C6–C7
ꢁ
ꢁ
ꢁ
1.521(6)
1.547(7)
1.501(7)
1.218(6)
1.464(7)
1.324(6)
1.507(6)
1.509(6)
1.513(6)
1.528(6)
1.504(6)
1.544(5)
1.529(6)
1.546(6)
1.568(7)
1.521(6)
1.514(6)
1.513(6)
1.536(7)
1.549(7)
1.521(6)
1.527(7)
1.555(7)
1.435(7)
1.525(7)
C1 –C2
1.495(6)
Space group
Unit cell dimensions
ꢁ
C1 –C10
1.543(6)
1.495(7)
1.193(6)
1.485(7)
1.354(6)
1.519(7)
1.507(6)
1.526(6)
1.536(5)
1.534(6)
1.558(6)
1.553(6)
1.532(6)
1.537(6)
1.557(6)
1.522(6)
1.536(6)
1.548(6)
1.533(6)
1.522(6)
1.537(7)
1.533(7)
1.437(6)
1.514(7)
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C2 –C3
˚
a (A)
6.382(2)
12.841(5)
43.350(17)
3552(2)
8
ꢁ
C3 –O1
˚
b (A)
ꢁ
C3 –C4
˚
c (A)
Volume (A )
ꢁ
C4 –C5
˚
3
ꢁ
ꢁ
C5 –C6
Z
ꢁ
ꢁ
ꢁ
C5 –C10
3
Calculated density (Mg/m )
Radiation, wavelength (λ)
F(000)
Crystal size (mm)
θ range for data collection ( )
1.165
Mo Kα, 0.71073 A
ꢁ
ꢁ
ꢁ
C6 –C7
˚
ꢁ
C7–C8
C8–C14
C8–C9
C7 –C8
1368
ꢁ
C8 –C14
0.30 × 0.25 × 0.20
ꢁ
ꢁ
C8 –C9
◦
2.12–24.96
ꢁ
ꢁ
ꢁ
C9–C10
C9–C11
C10–C19
C11–C12
C12–C13
C13–C14
C13–C17
C13–C18
C14–C15
C15–C16
C16–C17
C17–O2
C17–C20
C9 –C10
Limiting indices
0 ≤ h ≤ 7, 0 ≤ k ≤ 15, 0 ≤ l
ꢁ
C9 –C11
≤
51
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C10 –C19
C11 –C12
C12 –C13
C13 –C14
C13 –C17
C13 –C18
C14 –C15
C15 –C16
Reflections collected/unique
Data/restraints/parameters
Absorption coefficient (mm 1)
Goodness-of-fit on F2
Final R-factor
3681/3602
3602/0/413
0.074
−
0.812
0.0479
0.0860
−0.13 < ꢀρ < 0.13
wR
˚
−3
Largest diff. peak and hole (e A
)
ꢁ
ꢁ
ꢁ
C16 –C17
C17 –O2
C17 –C20
ꢁ
ꢁ
Results and discussion
◦
Bond angles ( )
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C2–C1–C10
C3–C2–C1
O1–C3–C4
O1–C3–C2
C4–C3–C2
114.7(4)
110.7(5)
122.7(6)
121.4(6)
115.5(5)
124.3(5)
120.3(5)
123.9(5)
115.8(5)
112.6(4)
111.5(5)
112.5(4)
110.6(4)
108.7(4)
113.9(4)
115.1(4)
110.7(4)
111.2(4)
109.1(4)
109.3(4)
107.9(5)
110.3(4)
108.9(5)
114.5(4)
110.9(4)
108.2(4)
C2 –C1 –C10
114.8(4)
111.7(4)
122.4(5)
123.7(5)
113.9(5)
124.0(5)
119.9(5)
123.2(5)
116.9(5)
111.1(4)
112.1(4)
110.8(4)
108.8(4)
109.5(4)
113.9(4)
113.5(3)
109.4(4)
108.7(4)
108.8(4)
108.9(4)
109.1(4)
111.7(4)
109.6(4)
112.7(4)
111.5(4)
107.6(4)
ꢁ
The bond lengths and bond angles for non-
hydrogen atoms are given in Table 2. A general
view of the molecule indicating atomic numbering
scheme (thermal ellipsoid drawn at 50% probabil-
C3 –C2 –C1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
O1 –C3 –C4
O1 –C3 –C2
ꢁ
ꢁ
C4 –C3 –C2
ꢁ– ꢁ–
C5 C4 C3
–
–
C5 C4 C3
13
ꢁ ꢁ
C4 –C5 –C6
–C5–C6
ity) is shown in Fig. 1. In both the molecules,
the bond distances and angles agree well with the
values reported in the literature for some anal-
C4
ꢁ ꢁ
ꢁ
ꢁ
C4–C5–C10
C6–C5–C10
C5–C6–C7
C6–C7–C8
C14–C8–C7
C14–C8–C9
C7–C8–C9
C10–C9–C8
C4 –C5 –C10
ꢁ
ꢁ
ꢁ
ꢁ
C6 –C5 –C10
ꢁ
ꢁ
C5 –C6 –C7
4
–10
ꢁ ꢁ
ogous structures.
[
The bond lengths C3–C4
C6 –C7 –C8
ꢁ ꢁ
ꢁ
ꢁ
ꢁ
2
ꢁ
C14 –C8 –C7
1.464(7)] and C3 –C4 [1.481(7)] are greater than
ꢁ
ꢁ
C14 –C8 –C9
2
the standard C(sp )–C(sp ) value [1.447] and this
ꢁ
ꢁ
ꢁ
C7 –C8 –C9
ꢁ
ꢁ
ꢁ
could be due to large deviation of the oxygen
C10 –C9 –C8
ꢁ
ꢁ– ꢁ–
ꢁ
C10 C9 C11
–
–
C10 C9 C11
atoms attached to C3 and C3 [deviation being
−
ꢁ ꢁ
C8 –C9 –C11
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C8
–C9–C11
0.175 for O1 and 0.327 for O1 ).
ꢁ
ꢁ
C5–C10–C9
C5 –C10 –C9
ꢁ– ꢁ–
C5 C10 C1
In molecule I, the ring A adopts a distorted
C5 C10 C1
–
–
ꢁ ꢁ
C9 –C10 –C1
–C10–C1
half-chair conformation [asymmetry parameter,
C9
ꢁ ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
1
4
C5–C10–C19
C9–C10–C19
C1–C10–C19
C12–C11–C9
C13–C12–C11
C14–C13–C12
C5 –C10 –C19
ꢀ
C (C1–C2) = 8.48; ꢀC (C1) = 14.34].
2
s
ꢁ
ꢁ
ꢁ
ꢁ
C9 –C10 –C19
Ring B exists in normal chair conformation
ꢀC (C5–C10) = 1.20; ꢀC (C7) = 3.60]. Ring
C1 –C10 –C19
ꢁ ꢁ
[
C12 –C11 –C9
C13 –C12 –C11
C14 –C13 –C12
2
s
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C also depicts a normal chair conformation
14
[
ꢀC (C9–C11) = 3.89; ꢀC (C9) = 2.64]. The
2
s

2
86
Verma, Jasrotia, and Bhat
Table 2. Continued.
ꢁ
ꢁ
chair conformation [ꢀC (C11 –C12 ) = 2.69;
2
ꢁ
ꢀ
C (C11 ) = 0.83]. The five-membered ring
s
Molecule I
Molecule II
D depicts a distorted half-chair conformation
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C14–C13–C17
C12–C13–C17
C14–C13–C18
C12–C13–C18
C17–C13–C18
C8–C14–C13
C8–C14–C15
C13–C14–C15
C14–C15–C16
C15–C16–C17
O2–C17–C20
O2–C17–C13
C20–C17–C13
O2–C17–C16
C20–C17–C16
C13–C17–C16
102.5(4)
116.9(5)
112.0(5)
109.8(5)
107.3(5)
114.8(4)
119.4(4)
104.1(4)
104.7(4)
106.9(5)
107.5(4)
115.0(5)
115.4(5)
105.9(5)
109.4(6)
103.1(5)
C14 –C13 –C17
100.5(3)
117.6(4)
111.2(4)
109.6(3)
109.9(4)
114.1(4)
119.5(4)
104.1(4)
103.9(4)
107.4(4)
106.8(4)
112.2(4)
114.1(4)
107.9(4)
112.2(4)
103.6(4)
[ꢀC2(C13 –C14 ) = 9.36], with phase angle of
C12 –C13 –C17
◦
pseudorotation, ꢀ = −4.66 and maximum angle
C14 –C13 –C18
◦
of torsion, ϕ = −45.4 .
m
C12 –C13 –C18
ꢁ
ꢁ
In orthorhombic space group P2 2 2 , the
C17 –C13 –C18
1 1 1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C8 –C14 –C13
molecules of 17α-hydroxy-17-methylandrost-4-
ene-17-one are linked by paired O–H· · ·O hydro-
C8 –C14 –C15
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C13 –C14 –C15
2
2
16
gen bonds into C (6) graph set, where C refers
C14 –C15 –C16
C15 –C16 –C17
for chain. The crystal structure is stabilized by
O–H· · ·O and C–H· · ·O hydrogen bonds and the
hydrogen-bonding network is shown in Fig. 2.
Both the crystallographic independentmoleculesI
and II are linked to one another through O–H· · ·O
hydrogen bonds. The long linear chains bonded
through O2–H2· · ·O1 and O2 –H2 · · ·O1 inter-
molecular hydrogen interactions have been ob-
served. For both the molecules, the O2 atom acts
as hydrogen donor whereas the O1 acts as accep-
tor atom. In molecule I, the atom C16 at (x, y, z)
acts as hydrogen bond donor to the O3 atom of the
water at (x−1/2−1, −y+1/2+1, −z+1), and thus
makes C–H· · ·O intermolecular interaction. The
H· · ·A distance (d) in both the O–H· · ·O inter-
molecular interactions is almost equal and it leads
that the crystal can be pictorially described as
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
O2 –C17 –C20
O2 –C17 –C13
ꢁ
ꢁ
ꢁ
C20 –C17 –C13
ꢁ
ꢁ
ꢁ
O2 –C17 –C16
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C20 –C17 –C16
C13 –C17 –C16
ꢁ
ꢁ
ꢁ
five-membered ring D occurs in a distorted half-
chair conformation [ꢀC (C13–C14) = 7.15],
2
◦
with phase angle of pseudorotation, ꢀ = −3.65
◦
15
and maximum angle of torsion, ϕ = −43.7 .
m
In molecule II, ring A exists in dis-
torted half-chair conformation [asymmetry
ꢁ
ꢁ
ꢁ
parameter,ꢀC (C1 –C2 ) = 8.25; ꢀC (C1 ) =
2
s
1
7.22]. Ring B adopts a symmetrical chair con-
ꢁ
ꢁ
ꢁ
formation [ꢀC (C5 –C10 ) = 1.66; ꢀC (C5 ) =
2
s
1
.57]. Ring C also occurs in symmetrical
Fig. 1. General view of the molecules (thermal ellipsoids drawn at 50% probability).

1
7α-hydroxy-17-methylandrost-4-ene-17-one
287
Fig. 2. Depiction of intermolecular hydrogen bonding interactions.
being formed by chains of molecules. The geom-
etry of O–H· · ·O and C–H· · ·O hydrogen bonds
is presented below:
References
1
2
3
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2
˚
˚
–
◦
H· · ·A (A) D· · ·A (A)
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(i)
O2–H2· · ·O1
2.07(5)
2.08(5)
2.57(1)
2.884(6)
2.901(6)
3.406(10)
158(5)
169(5)
144(5)
ꢁ
ꢁ
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7
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Supplementary material CCDC-217672 contains the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge at www.ccdc.cam.an.uk/uk/conts/retrieving.html or
from the Cambridge Crystallographic Data Centre (CCDC), 12
Union Road, Cambridge CB2 1EZ, United Kingdom; Fax: +44(O)
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Acknowledgments
The corresponding author (Rajnikant) is
thankful to the UGC, New Delhi for the financial
support under its DRS research project.
1
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