17-Deoxoestrone [estra-1,3,5(10)-trien-3-ol]–methanol (3/1)

Kamal Aziz Ketuly; A Hamid A Hadi; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536811013651

. 2011 Apr 16;67(Pt 5):o1160–o1161. doi: 10.1107/S1600536811013651

17-Deoxoestrone [estra-1,3,5(10)-trien-3-ol]–methanol (3/1)

Kamal Aziz Ketuly ^a,^‡, A Hamid A Hadi ^a, Seik Weng Ng ^a, Edward R T Tiekink ^a,^*

PMCID: PMC3089339 PMID: 21754468

Abstract

Three independent molecules of the title estrone derivative and a molecule of methanol comprise the asymmetric unit of the title compound [systematic name: 13-methyl-6,7,8,9,11,12,13,14,15,16-decahydrocyclopenta[a]phenanthren-3-ol–methanol (3/1)], 3C₁₈H₂₄O·CH₃OH. Two of the estrone molecules exhibit 50:50 disorder (one displays whole-molecule disorder and the other partial disorder in the fused five- and six-membered rings) so that five (partial) molecular conformations are discernable. The conformation of the six-membered ring abutting the aromatic ring is close to a half-chair in all five components. The conformation of the six-membered ring fused to the five-membered ring is based on a chair with varying degrees of distortion ranging from minor to significant. Two distinct conformations are found for the five-membered ring: in four molecules, the five-membered ring is twisted about the bond linking it to the six-membered ring, and in the other, the five-membered ring is an envelope with the quaternary C atom being the flap atom. The crystal packing features O—H⋯O hydrogen bonding whereby the four molecules comprising the asymmetric unit are linked into a supramolecular chain along the b axis.

Related literature

For the original synthesis, see: Huang-Minlon (1949 ▶). For geometric and structural features for a series of cholestane derivatives, see: Rajnikant et al. (2006 ▶). For background to steroidal estrogen boronic acids and boronates, see: Ketuly & Hadi (2010 ▶). For related structures see: Ketuly et al. (1997 ▶, 2010 ▶).

Experimental

Crystal data

3C₁₈H₂₄O·CH₄O
M _r = 801.16
Monoclinic,
a = 24.3084 (16) Å
b = 7.7235 (5) Å
c = 26.6479 (18) Å
β = 114.292 (1)°
V = 4560.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 100 K
0.35 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.976, T _max = 0.993
21707 measured reflections
5612 independent reflections
4481 reflections with I > 2σ(I)
R _int = 0.050

Refinement

R[F ² > 2σ(F ²)] = 0.052
wR(F ²) = 0.141
S = 1.02
5612 reflections
616 parameters
234 restraints
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶), DIAMOND (Brandenburg, 2006 ▶) and QMOL (Gans & Shalloway, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811013651/hb5844sup1.cif

e-67-o1160-sup1.cif^{(54.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811013651/hb5844Isup2.hkl

e-67-o1160-Isup2.hkl^{(274.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O3	0.84	1.83	2.662 (3)	170
O2—H2⋯O4	0.84	1.82	2.655 (4)	170
O3—H3⋯O2	0.84	1.88	2.711 (3)	173
O4—H4⋯O1ⁱ	0.84	1.90	2.736 (4)	178

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the University of Malaya for support and greatly appreciate UMRG grant No. RG035/10BIO.

supplementary crystallographic information

Comment

The title estrone, (I), has been prepared by a modified procedure from Huang-Minlon (1949) as a precursor for the synthesis of steroidal estrogen boronic acids and boronates (Ketuly & Hadi, 2010). Related structures have been reported (Ketuly et al., 1997; Ketuly et al., 2010) as has a systematic evaluation of geometric and structural features for a series of cholestane derivatives (Rajnikant et al., 2006). Herein, the crystal and molecular structure of (I) is described.

Three independent estrone molecules, Figs 1 - 3, and a solvent methanol molecule comprise the asymmetric unit of (I). The first independent molecule exhibits whole molecule disorder pivoted on the O1 atom. As seen from the overlay diagram, Fig. 4, the two components of equal weight, i.e. shown as red and green, have almost identical conformations. Referring to the Scheme for numbering of the rings, the six-membered ring B, being fused to an aromatic ring, has an half-chair conformation, six-membered ring C has a slightly twisted chair conformation, and five-membered ring C is twisted on the bond linking it to the six-membered ring. Disorder is also evident in the second independent molecule. In this case, the 50:50 disorder is restricted to rings C and D. As shown in pink and blue in Fig. 4, the rings have distinct conformations. For the molecule illustrated in pink, ring B is an half-chair and the conformation of ring C is that of a twisted chair. Ring D is an envelope on the quaternary-C29 atom. In the second disordered conformation, ring B is an half-chair and ring C is a slightly twisted chair. Ring D is distinct from that in the first orientation in that is adopts a twisted conformation about the C25—C29 bond. The third independent molecule, shown as light-blue in Fig. 4, is different from the other molecules in that ring B is a slightly twisted half-chair, ring C is a slightly twisted chair, and ring C is twisted about the C43—C47 bond.

In the crystal packing, the four independent molecules are connected via a sequence of O—H···O hydrogen bonds, Table 1. These link molecules into a supramolecular chain along the b axis, Fig. 5.

Experimental

The title compound (I) was prepared by a modified procedure from Huang-Minlon (1949) Estrone (1.5 g) was dissolved in diethylene glycol (40 ml), with heating and stirring in an oil bath at 388–393 K. Hydrazine hydrate (98–100%) was added in four 3 ml portions at 15 min intervals. During this time stirring and heating was continued and the flask connected to a drying tube. While the temperature was raised to 423 K, nitrogen was bubbled through the reaction mixture to remove excess reagent and water as by-product. When most of the reagent had been evaporated, KOH pellets (9.6 g) were added. The flask was then fitted with a 50 cm air condenser (with a drying tube), and the reaction mixture was refluxed for 2 h under nitrogen. The cooled basic reaction mixture was diluted with water and extracted three times with ether, and each extract was washed five times with water. The ether extracts were dried under vacuum and the residue crystallized from MeOH/water, yielding colourless crystals (1.305 g, 91%), M.pt. 401–403 K. This product was recrystallized three times from MeOH/water, yielding (I). M.pt. 407–408 K, (Lit. 407–407.5 K (Huang-Minlon, 1949)).