N,N′-Bis(3β-acet­oxy-5α-cholest-6-yl­idene)hydrazine

Zishan Tabassum; Othman Sulaiman; M N Mohamad Ibrahim; Ching Kheng Quah; Hoong-Kun Fun

doi:10.1107/S1600536811003254

. 2011 Jan 29;67(Pt 2):o522–o523. doi: 10.1107/S1600536811003254

N,N′-Bis(3β-acetoxy-5α-cholest-6-ylidene)hydrazine

Zishan Tabassum ^a, Othman Sulaiman ^a, M N Mohamad Ibrahim ^b, Ching Kheng Quah ^c,^‡, Hoong-Kun Fun ^c,^*,^§

PMCID: PMC3051532 PMID: 21523172

Abstract

The asymmetric unit of the title compound, C₅₈H₉₆N₂O₄, contains two crystallographically independent molecules. All cyclohexane rings are in chair conformations, while the furan ring is in an envelope conformation in one molecule and a twist conformation in the other. Two acetaldehyde and one isobutane groups are disordered over two orientations with refined site occupancies of 0.940 (4):0.060 (4) and 0.791 (7):0.209 (7), respectively. In the crystal, molecules are stacked along the a axis through van der Waals interactions.

Related literature

For general background to the biological activity of steroids, see: Li et al. (1998 ▶); Fink et al. (1999 ▶). For the pharmacological activity of cholesterol derivatives, see: Khan et al. (2007 ▶); Shamsuzzaman et al. (2010 ▶). For the preparation of the title compound, see: Anagnostopoulos & Fieser (1954 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₅₈H₉₆N₂O₄
M _r = 885.37
Triclinic,
a = 9.5892 (4) Å
b = 16.1622 (6) Å
c = 19.5255 (7) Å
α = 65.832 (2)°
β = 89.562 (2)°
γ = 81.364 (2)°
V = 2724.70 (18) Å³
Z = 2
Cu Kα radiation
μ = 0.50 mm⁻¹
T = 100 K
0.55 × 0.47 × 0.31 mm

Data collection

Bruker APEX DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.736, T _max = 0.860
109300 measured reflections
15864 independent reflections
15509 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.057
wR(F ²) = 0.151
S = 1.19
15864 reflections
1266 parameters
258 restraints
H-atom parameters constrained
Δρ_max = 0.76 e Å⁻³
Δρ_min = −0.78 e Å⁻³
Absolute structure: Flack (1983 ▶), 6966 Friedel pairs
Flack parameter: −0.04 (17)

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811003254/rz2546sup1.cif

e-67-0o522-sup1.cif^{(87.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811003254/rz2546Isup2.hkl

e-67-0o522-Isup2.hkl^{(775.3KB, hkl)}

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

Acknowledgments

We would like to acknowledge Universiti Sains Malaysia (USM) for postdoctoral fellowship support for Dr Zishan Tabassum and for supporting under research grant No. 304/PTEKIND/639062. HKF and CKQ thank USM for the Research University Grant (No. 1001/PFIZIK/811160).

supplementary crystallographic information

Comment

Medicinal chemistry of steroids has become a matter of immense interest in recent past due to their biological applications (Li et al., 1998; Fink et al., 1999). The synthesis of cholesterol amine derivatives have also become of interest in recent years because their biocompatibility. Cholesterol intermediates and their derivatives are found to be pharmacologically active (Khan et al., 2007; Shamsuzzaman et al., 2010) which prompted us to synthesize a cholesterol derivative of hydrazine. Herein the synthesis and crystal structure of the title compound are reported.

The asymmetric unit (Fig. 1) contains two independent molecules, A and B. Each molecule is constructed from the fusion of six cyclohexane rings, A, B, C, D, E and F; and two furan rings, G and H. The absolute configuration at atoms C3, C4, C7, C9, C13, C32, C33, C36, C38, C42 is S and at atoms C12, C16, C17, C41, C45, C46 is R (see scheme, Fig. 2 and Fig. 3). The rings A/B, B/C, C/G, D/E, E/F and F/H are trans-fused. All cyclohexane rings (A/B/C/D/E/F) are in chair conformations. In molecule A (Fig. 2), the two furan rings, C1A-C3A/C16A/C17A and C30A-C32A/C45A/C46A are in envelope conformations, puckering parameters Q = 0.460 (3) Å; Θ = 288.6 (4)° (Cremer & Pople, 1975) with atom C16A at the flap; and Q = 0.466 (3) Å; Θ = 283.1 (3)° with atom C45A at the flap, respectively. In molecule B (Fig. 3), the two furan rings, C1B-C3B/C16B/C17B and C30B-C32B/C45B/C46B are in twist conformations, puckering parameters Q = 0.455 (3) Å; Θ = 273.4 (4)° with twisted on atoms C3B and C16B; and Q = 0.471 (3) Å; Θ = 272.7 (3)° with twisted on atoms C32B and C45B, respectively. The acetaldehyde group (O2/C28/C29) in both molecules and the isobutane (C21B-C24B) group in molecule B are disordered over two positions with refined site occupancies of 0.940 (4):0.060 (4) and 0.791 (7):0.209 (7), respectively.

In the crystal (Fig.4), molecules are stacked along the a axis and there is no significant hydrogen bond observed in this compound.

Experimental

The title compound was prepared by reaction of 3β-acetoxy-5α-cholestan-6-one (0.0022 mol) (Anagnostopoulos & Fieser, 1954) with hydrazine hydrate (1.5 ml) in presence of glacial acetic acid (10 ml). Reaction progress was monitored by TLC. After refluxing the reaction mixture for 5 h, the solution was cooled and poured into ice cold water. The solution was extracted with chloroform; the organic layer was washed with water, sodium bicarbonate solution (5%) and passed through anhydrous sodium sulphate. The solution was concentrated under reduced pressure and the residue was crystallized from a chloroform–methanol (1:1) v/v solution (yield 70%). M.p. 226°C.