3-(4-Chloro­phenyl­sulfon­yl)-8-methyl-1,3-diaza­spiro­[4.5]decane-2,4-dione

M Kalim Kashif; M Khawar Rauf; Michael Bolte; Shahid Hameed

doi:10.1107/S1600536809027482

. 2009 Jul 18;65(Pt 8):o1893. doi: 10.1107/S1600536809027482

3-(4-Chlorophenylsulfonyl)-8-methyl-1,3-diazaspiro[4.5]decane-2,4-dione

M Kalim Kashif ^a, M Khawar Rauf ^a, Michael Bolte ^b, Shahid Hameed ^a,^*

PMCID: PMC2977302 PMID: 21583583

Abstract

In the title compound, C₁₅H₁₇ClN₂O₄S, the atoms in the hydantoin ring are coplanar (r.m.s. deviation = 0.006 Å). The crystal structure is stabilized by intermolecular N—H⋯O hydrogen bonds which link the molecules into centrosymmetric dimers. The dihedral angle subtended by the 4-chlorophenyl group with the plane passing through the hydantoin unit is 82.98 (4)°. The cyclohexyl ring adopts an ideal chair conformation.

Related literature

For background to diabetes and its treatment, see: Tiwari & Rao (2002 ▶); DeFronzo (1999 ▶); Feinglos & Bethel (1998 ▶); Murakami et al., (1997 ▶). We have synthesized a number of N-arylsulfonylimidazolidine-2,4-diones and evaluated their antidiabetic activity, see: Hussain et al. (2009a ▶,b ▶); Kashif, Ahmad et al. (2008 ▶); Kashif, Hussain et al. (2008 ▶); For related structures, see: Gauthier et al. (1997 ▶); Kashif, Hussain et al. (2008 ▶).

Experimental

Crystal data

C₁₅H₁₇ClN₂O₄S
M _r = 356.82
Monoclinic,
a = 6.1722 (4) Å
b = 17.4561 (12) Å
c = 15.1355 (9) Å
β = 94.460 (5)°
V = 1625.80 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.38 mm⁻¹
T = 173 K
0.38 × 0.36 × 0.33 mm

Data collection

Stoe IPDS-II two-circle diffractometer
Absorption correction: multi-scan (MULABS; Spek, 2009 ▶; Blessing, 1995 ▶) T _min = 0.868, T _max = 0.884
19365 measured reflections
3203 independent reflections
2983 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.081
S = 1.04
3203 reflections
213 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.38 e Å⁻³

Data collection: X-AREA (Stoe & Cie, 2001 ▶); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809027482/hg2537sup1.cif

e-65-o1893-sup1.cif^{(20KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809027482/hg2537Isup2.hkl

e-65-o1893-Isup2.hkl^{(157.2KB, 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
N2—H2⋯O4ⁱ	0.84 (2)	2.04 (2)	2.8763 (15)	171.5 (19)

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Symmetry code: (i) Inline graphic .

Acknowledgments

MKR is grateful to the HEC-Pakistan for financial support for a PhD program under scholarship No. [ILC–0363104].

supplementary crystallographic information

Comment

Diabetes is one of the major causes of disease related deaths in these modern times and the people in South-east Asia and Western Pacific are being the most at risk (Tiwari et al., 2002). To cure the disease sulfonyl ureas are the most frequently used antidiabetic drugs (DeFronzo, 1999; Feinglos & Bethel, 1998). An important complication related to this disease is the cataract formation and imidazolidine-2,4-diones have been found as aldose reductase inhibitors (Murakami et al., 1997). The combination of the two scaffolds, i.e. the sulfonyl urea and the imidazolidine-2,4-dione, in one molecule may be a useful combination to cure the disease and associated complications, especially the cataract formation. With this hypothesis in mind, we synthesized a number of N-arylsulfonylimidazolidine-2,4-diones and evaluated their antidiabetic activity (Hussain et al., 2009a,b; Kashif, Ahmad et al., 2008; Kashif, Hussain et al., 2008). In the present paper, we report the synthesis and crystal structure of the title compound. The bond lengths and angles within the hydantoin (2,4-imidazolidenedione) moiety are normal, typical of those observed in cyclohexanespiro-5'-hydantoin (Gauthier et al., 1997; Kashif & Hussain et al., 2008). The hydantoin unit is exactly planar (r.m.s. deviation 0.006 Å). The cyclohexane ring has adopted chair conformation, with endocyclic torsion-angle magnitudes of 54.87 (16)–56.26 (16)°. The C1—O3 and C3—O4 bond lengths are 1.1985 (17) and 1.2242 (16) Å, respectively, which are close to the standard value for CO(1.20 Å). The dihedral angle subtended by the p-chlorophenyl group with the plane passing through the hydantoin moiety is 82.98 (4)°. Intermolecular N—H···O hydrogen bonds link the molecules to form centrosymmetric dimers.

Experimental

Substituted cyclohexanone (0.1 mol) and ammonium carbonate (0.6 mol) were placed in a 100 ml round bottom flask. Potassium cyanide (0.1 mol) was dissolved in aqueous ethanol (60%) and added to the reaction flask. The mixture was heated on an oil bath at 328–333 K until the reaction was complete (monitored by TLC). After cooling to room temperature, the reaction mixture was concentrated and acidified using conc. HCl. The resulting precipitates were filtered, dissolved in saturated NaOH_(aq) solution and extracted with diethyl ether (2 × 25 ml). The aqueous layer was acidified to precipitate 8-substituted-1,3-diazaspiro[4.5]decane-2,4-dione, which was filtered and recrystallized from ethanol/water. 8-substituted-1,3-diazaspiro[4.5]decane-2,4-dione (4.8 mmol) in CH₂Cl₂ (20 ml) was stirred with triethyl amine (4.8 mmol) and catalytic amounts of DMAP. The aryl sulfonyl chloride (5.8 mmol) in CH₂Cl₂ (10 ml) was added drop wise and the reaction mixture stirred at room temperature. After completion of the reaction (TLC), the mixture was diluted with 1 M HCl (20 ml) and extracted with CH₂Cl₂ (3 × 25 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Recrystallization of the residue from ethyl acetate afforded the colourless plate-like crystals, suitable for X-ray analysis.