9α-Bromo analog of beclometasone dipropionate monohydrate

Kamal Aziz Ketuly; A Hamid A Hadi; Seik Weng Ng

doi:10.1107/S1600536809025975

. 2009 Jul 11;65(Pt 8):o1821. doi: 10.1107/S1600536809025975

9α-Bromo analog of beclometasone dipropionate monohydrate

Kamal Aziz Ketuly ^a, A Hamid A Hadi ^a, Seik Weng Ng ^a,^*

PMCID: PMC2977184 PMID: 21583523

Abstract

In the crystal structure of (8S,9R,10S,11S,13S,14S,16S,17R)-9α-bromo-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate monohydrate, C₂₈H₃₇BrO₇·H₂O, which has a 9α-Br atom in place of the 9α-Cl atom of monohydrated beclometasone dipropionate, one six-membered ring is planar (r.m.s. deviation = 0.02 Å) owing to its 1,4-diene-3-one composition, whereas the two other six-membered rings each have a chair conformation. The organic molecule and water molecules engage in hydrogen-bonding interactions, generating a helical chain running along the c axis of the orthorhombic unit cell.

Related literature

For the NMR data and the crystal structure of the asthma drug beclometasone dipropionate monohydrate, see: Othman et al. (2008 ▶); Duax et al. (1981 ▶). The two compounds are isostructural.

Experimental

Crystal data

C₂₈H₃₇BrO₇·H₂O
M _r = 583.50
Orthorhombic,
a = 11.9565 (2) Å
b = 14.1329 (2) Å
c = 16.1648 (3) Å
V = 2731.53 (8) Å³
Z = 4
Mo Kα radiation
μ = 1.55 mm⁻¹
T = 140 K
0.40 × 0.08 × 0.08 mm

Data collection

Bruker SMART APEX diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.611, T _max = 0.746 (expected range = 0.723–0.883)
18917 measured reflections
6226 independent reflections
5575 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.026
wR(F ²) = 0.055
S = 0.96
6226 reflections
351 parameters
4 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.25 e Å⁻³
Absolute structure: Flack (1983 ▶), 2717 Friedel pairs
Flack parameter: 0.001 (5)

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: X-SEED (Barbour, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809025975/tk2488sup1.cif

e-65-o1821-sup1.cif^{(26.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809025975/tk2488Isup2.hkl

e-65-o1821-Isup2.hkl^{(304.8KB, 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
O2—H2⋯O1w	0.83 (1)	1.93 (1)	2.759 (2)	173 (2)
O1w—H11⋯O5	0.84 (1)	2.06 (1)	2.859 (2)	159 (3)
O1w—H12⋯O7ⁱ	0.84 (1)	2.03 (1)	2.854 (2)	168 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank the University of Malaya for supporting this study.

supplementary crystallographic information

Experimental

17α,21-Dihydroxy-16β-methylpregna-1,4,9-triene-3,20-dionedipropionate (5.5 g) was reacted with bromodan (1,3-dibromo-5,5-dimethylhydantion) (4.8 g) to give a yellow product (6.6 g). TLC showed one major product and five minor ones. The major product (3.0 g) was initially recrystallized three times, once from chloroform-methanol (1:2 v/v), and the second and third times from hexane-methanol (1:1 v/v). The recovered material (1.8 g). was then divided for two different recrystallizations.

Recrystallization form ethyl acetate-methanol (1:9 v/v) gave a white powder, m.p. 453–455 K. Elemental analysis: Calc. for C₂₈H₃₇BrO₇ (mol. wt. 564): C 59.47, H 6.59, Br 14.13%. Found: C 59.3, H 6.57, Br 13.83%.

Recrystallization from methanol water gave colorless crystals, m.p. 460–461 K. Elemental analysis: Calc. for C₂₂H₃₇BrO₇^.H₂O (mol. wt. 582): C 57.64, H 6.69, Br 13.70%. Found: C 57.68, H 6.78, Br 13.46%. The water molecule was detected from the ¹H-NMR spectrum. Thermogravimetric analysis showed a peak at 365 K that corresponded to the loss of water.