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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1893.
Published online 2009 July 18. doi:  10.1107/S1600536809027482
PMCID: PMC2977302

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

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 [triangle]); DeFronzo (1999 [triangle]); Feinglos & Bethel (1998 [triangle]); Murakami et al., (1997 [triangle]). We have synthesized a number of N-aryl­sulfonyl­imidazolidine-2,4-diones and evaluated their anti­diabetic activity, see: Hussain et al. (2009a [triangle],b [triangle]); Kashif, Ahmad et al. (2008 [triangle]); Kashif, Hussain et al. (2008 [triangle]); For related structures, see: Gauthier et al. (1997 [triangle]); Kashif, Hussain et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1893-scheme1.jpg

Experimental

Crystal data

  • C15H17ClN2O4S
  • M r = 356.82
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1893-efi1.jpg
  • 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 [triangle]; Blessing, 1995 [triangle]) 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
  • Δρmax = 0.33 e Å−3
  • Δρmin = −0.38 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

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

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.

Refinement

H atom on the N atom was refined isotropically. Other H atoms were placed in idealized positions and treated as riding atoms with C—H distance in the range 0.95–1.00 Å and Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl).

Figures

Fig. 1.
Molecular structure of the title compound with displacement ellipsoids at the 50% probability level showing atom-labelling scheme.
Fig. 2.
Partial packing diagram of (I) with view onto the ac plane. Hydrogen bonds shown as dashed lines.

Crystal data

C15H17ClN2O4SF(000) = 744
Mr = 356.82Dx = 1.458 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 15156 reflections
a = 6.1722 (4) Åθ = 3.0–26.3°
b = 17.4561 (12) ŵ = 0.38 mm1
c = 15.1355 (9) ÅT = 173 K
β = 94.460 (5)°Block, colourless
V = 1625.80 (18) Å30.38 × 0.36 × 0.33 mm
Z = 4

Data collection

Stoe IPDS-II two-circle diffractometer3203 independent reflections
Radiation source: fine-focus sealed tube2983 reflections with I > 2σ(I)
graphiteRint = 0.040
ω scansθmax = 26.0°, θmin = 2.9°
Absorption correction: multi-scan (MULABS; Spek, 2009; Blessing, 1995)h = −7→7
Tmin = 0.868, Tmax = 0.884k = −21→21
19365 measured reflectionsl = −16→18

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.081w = 1/[σ2(Fo2) + (0.038P)2 + 0.7834P] where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
3203 reflectionsΔρmax = 0.33 e Å3
213 parametersΔρmin = −0.38 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0255 (15)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
S10.36511 (5)0.371795 (19)0.23107 (2)0.02303 (12)
Cl10.79176 (9)0.63621 (3)0.02791 (3)0.05300 (16)
N10.50643 (18)0.37056 (6)0.33214 (7)0.0219 (2)
N20.62920 (18)0.41517 (6)0.46472 (7)0.0220 (2)
H20.641 (3)0.4423 (11)0.5109 (14)0.042 (5)*
O10.14563 (16)0.39092 (7)0.24485 (7)0.0341 (3)
O20.41742 (18)0.30140 (6)0.19042 (7)0.0313 (2)
O30.7072 (2)0.25599 (6)0.33154 (7)0.0384 (3)
O40.37659 (16)0.48815 (6)0.38160 (6)0.0289 (2)
C10.6589 (2)0.31459 (8)0.36628 (9)0.0234 (3)
C20.7484 (2)0.34352 (7)0.45728 (8)0.0200 (3)
C30.4938 (2)0.43204 (7)0.39448 (8)0.0212 (3)
C40.9937 (2)0.35863 (9)0.45695 (9)0.0277 (3)
H4A1.06890.31090.44170.033*
H4B1.02020.39760.41150.033*
C51.0850 (2)0.38688 (9)0.54830 (10)0.0303 (3)
H5A1.24400.39400.54780.036*
H5B1.01980.43720.56050.036*
C61.0389 (2)0.33104 (9)0.62226 (10)0.0313 (3)
H61.11360.28160.61070.038*
C70.7954 (3)0.31502 (9)0.62127 (9)0.0302 (3)
H7A0.71930.36250.63680.036*
H7B0.76990.27600.66680.036*
C80.7004 (2)0.28651 (8)0.53063 (9)0.0284 (3)
H8A0.54130.28000.53170.034*
H8B0.76410.23600.51790.034*
C91.1307 (3)0.36103 (12)0.71245 (12)0.0472 (4)
H9A1.28690.37040.71090.071*
H9B1.10670.32290.75830.071*
H9C1.05730.40890.72600.071*
C110.4850 (2)0.44792 (8)0.17624 (8)0.0228 (3)
C120.6817 (2)0.43427 (8)0.13975 (9)0.0286 (3)
H120.75020.38560.14600.034*
C130.7761 (2)0.49288 (10)0.09407 (10)0.0340 (3)
H130.91090.48510.06910.041*
C140.6711 (3)0.56299 (9)0.08531 (9)0.0332 (3)
C150.4758 (3)0.57708 (9)0.12184 (10)0.0352 (3)
H150.40750.62570.11520.042*
C160.3816 (2)0.51863 (8)0.16838 (10)0.0295 (3)
H160.24840.52690.19440.035*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.02463 (19)0.02646 (19)0.01742 (17)−0.00340 (12)−0.00210 (12)−0.00176 (12)
Cl10.0750 (3)0.0439 (3)0.0392 (2)−0.0247 (2)−0.0012 (2)0.01235 (18)
N10.0264 (6)0.0221 (6)0.0168 (5)0.0020 (4)−0.0016 (4)−0.0026 (4)
N20.0249 (6)0.0227 (6)0.0179 (5)0.0060 (4)−0.0015 (4)−0.0051 (4)
O10.0235 (5)0.0503 (7)0.0281 (5)−0.0030 (5)−0.0013 (4)0.0017 (5)
O20.0438 (6)0.0258 (5)0.0233 (5)−0.0057 (4)−0.0036 (4)−0.0056 (4)
O30.0607 (7)0.0273 (5)0.0261 (5)0.0145 (5)−0.0041 (5)−0.0077 (4)
O40.0328 (5)0.0288 (5)0.0241 (5)0.0120 (4)−0.0042 (4)−0.0049 (4)
C10.0301 (7)0.0215 (7)0.0187 (6)0.0018 (5)0.0021 (5)0.0001 (5)
C20.0242 (6)0.0185 (6)0.0173 (6)0.0032 (5)0.0017 (5)−0.0010 (5)
C30.0215 (6)0.0236 (6)0.0186 (6)0.0005 (5)0.0019 (5)−0.0032 (5)
C40.0232 (7)0.0355 (8)0.0250 (7)0.0049 (6)0.0062 (5)0.0005 (6)
C50.0192 (6)0.0401 (8)0.0314 (8)−0.0007 (6)0.0011 (5)−0.0038 (6)
C60.0346 (8)0.0340 (8)0.0239 (7)0.0101 (6)−0.0063 (6)−0.0037 (6)
C70.0417 (8)0.0309 (8)0.0178 (6)−0.0053 (6)0.0005 (6)0.0042 (5)
C80.0377 (8)0.0253 (7)0.0218 (7)−0.0070 (6)−0.0008 (6)0.0038 (5)
C90.0475 (10)0.0605 (11)0.0313 (9)0.0052 (8)−0.0122 (7)−0.0098 (8)
C110.0258 (6)0.0246 (6)0.0171 (6)−0.0014 (5)−0.0033 (5)−0.0012 (5)
C120.0291 (7)0.0298 (7)0.0266 (7)0.0025 (6)0.0008 (6)0.0016 (6)
C130.0325 (8)0.0411 (9)0.0286 (8)−0.0050 (6)0.0035 (6)0.0022 (6)
C140.0457 (9)0.0315 (8)0.0210 (7)−0.0122 (6)−0.0068 (6)0.0032 (6)
C150.0470 (9)0.0254 (7)0.0313 (8)0.0018 (6)−0.0079 (7)0.0004 (6)
C160.0316 (7)0.0301 (7)0.0263 (7)0.0044 (6)−0.0023 (6)−0.0029 (6)

Geometric parameters (Å, °)

S1—O21.4225 (11)C6—C71.528 (2)
S1—O11.4262 (11)C6—C91.529 (2)
S1—N11.7011 (11)C6—H61.0000
S1—C111.7602 (14)C7—C81.5325 (19)
Cl1—C141.7447 (15)C7—H7A0.9900
N1—C11.4251 (17)C7—H7B0.9900
N1—C31.4352 (16)C8—H8A0.9900
N2—C31.3331 (17)C8—H8B0.9900
N2—C21.4599 (16)C9—H9A0.9800
N2—H20.84 (2)C9—H9B0.9800
O3—C11.1985 (17)C9—H9C0.9800
O4—C31.2242 (16)C11—C161.390 (2)
C1—C21.5294 (18)C11—C121.393 (2)
C2—C81.5369 (18)C12—C131.388 (2)
C2—C41.5373 (18)C12—H120.9500
C4—C51.533 (2)C13—C141.386 (2)
C4—H4A0.9900C13—H130.9500
C4—H4B0.9900C14—C151.387 (2)
C5—C61.528 (2)C15—C161.393 (2)
C5—H5A0.9900C15—H150.9500
C5—H5B0.9900C16—H160.9500
O2—S1—O1121.04 (7)C5—C6—H6107.9
O2—S1—N1105.08 (6)C7—C6—H6107.9
O1—S1—N1107.33 (6)C9—C6—H6107.9
O2—S1—C11109.29 (6)C6—C7—C8112.07 (12)
O1—S1—C11109.35 (7)C6—C7—H7A109.2
N1—S1—C11103.21 (6)C8—C7—H7A109.2
C1—N1—C3110.02 (10)C6—C7—H7B109.2
C1—N1—S1127.78 (9)C8—C7—H7B109.2
C3—N1—S1122.10 (9)H7A—C7—H7B107.9
C3—N2—C2114.60 (11)C7—C8—C2110.76 (11)
C3—N2—H2123.2 (13)C7—C8—H8A109.5
C2—N2—H2122.2 (13)C2—C8—H8A109.5
O3—C1—N1127.29 (12)C7—C8—H8B109.5
O3—C1—C2126.30 (12)C2—C8—H8B109.5
N1—C1—C2106.40 (10)H8A—C8—H8B108.1
N2—C2—C1101.73 (10)C6—C9—H9A109.5
N2—C2—C8111.87 (11)C6—C9—H9B109.5
C1—C2—C8111.12 (11)H9A—C9—H9B109.5
N2—C2—C4110.84 (11)C6—C9—H9C109.5
C1—C2—C4109.93 (11)H9A—C9—H9C109.5
C8—C2—C4111.02 (11)H9B—C9—H9C109.5
O4—C3—N2129.04 (12)C16—C11—C12121.78 (13)
O4—C3—N1123.73 (12)C16—C11—S1120.22 (11)
N2—C3—N1107.24 (11)C12—C11—S1117.98 (11)
C5—C4—C2110.19 (11)C13—C12—C11118.93 (14)
C5—C4—H4A109.6C13—C12—H12120.5
C2—C4—H4A109.6C11—C12—H12120.5
C5—C4—H4B109.6C14—C13—C12119.16 (14)
C2—C4—H4B109.6C14—C13—H13120.4
H4A—C4—H4B108.1C12—C13—H13120.4
C6—C5—C4112.28 (12)C13—C14—C15122.20 (14)
C6—C5—H5A109.1C13—C14—Cl1118.69 (13)
C4—C5—H5A109.1C15—C14—Cl1119.11 (12)
C6—C5—H5B109.1C14—C15—C16118.80 (14)
C4—C5—H5B109.1C14—C15—H15120.6
H5A—C5—H5B107.9C16—C15—H15120.6
C5—C6—C7110.42 (11)C11—C16—C15119.12 (14)
C5—C6—C9111.01 (14)C11—C16—H16120.4
C7—C6—C9111.56 (13)C15—C16—H16120.4
O2—S1—N1—C14.87 (13)C8—C2—C4—C5−56.08 (15)
O1—S1—N1—C1134.92 (12)C2—C4—C5—C656.26 (16)
C11—S1—N1—C1−109.63 (12)C4—C5—C6—C7−55.42 (16)
O2—S1—N1—C3−179.06 (10)C4—C5—C6—C9−179.68 (13)
O1—S1—N1—C3−49.01 (12)C5—C6—C7—C854.87 (16)
C11—S1—N1—C366.44 (11)C9—C6—C7—C8178.81 (13)
C3—N1—C1—O3179.43 (14)C6—C7—C8—C2−55.61 (16)
S1—N1—C1—O3−4.1 (2)N2—C2—C8—C7−68.41 (15)
C3—N1—C1—C20.01 (14)C1—C2—C8—C7178.65 (12)
S1—N1—C1—C2176.48 (9)C4—C2—C8—C755.99 (15)
C3—N2—C2—C1−1.17 (14)O2—S1—C11—C16146.70 (11)
C3—N2—C2—C8−119.84 (12)O1—S1—C11—C1612.12 (13)
C3—N2—C2—C4115.67 (12)N1—S1—C11—C16−101.87 (11)
O3—C1—C2—N2−178.79 (14)O2—S1—C11—C12−31.78 (12)
N1—C1—C2—N20.63 (13)O1—S1—C11—C12−166.36 (11)
O3—C1—C2—C8−59.59 (19)N1—S1—C11—C1279.64 (11)
N1—C1—C2—C8119.83 (12)C16—C11—C12—C13−0.2 (2)
O3—C1—C2—C463.71 (18)S1—C11—C12—C13178.21 (11)
N1—C1—C2—C4−116.87 (12)C11—C12—C13—C14−0.6 (2)
C2—N2—C3—O4−178.83 (13)C12—C13—C14—C151.0 (2)
C2—N2—C3—N11.22 (15)C12—C13—C14—Cl1179.88 (11)
C1—N1—C3—O4179.32 (13)C13—C14—C15—C16−0.4 (2)
S1—N1—C3—O42.62 (18)Cl1—C14—C15—C16−179.32 (11)
C1—N1—C3—N2−0.73 (14)C12—C11—C16—C150.8 (2)
S1—N1—C3—N2−177.43 (9)S1—C11—C16—C15−177.62 (11)
N2—C2—C4—C568.89 (14)C14—C15—C16—C11−0.5 (2)
C1—C2—C4—C5−179.43 (11)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2···O4i0.84 (2)2.04 (2)2.8763 (15)171.5 (19)

Symmetry codes: (i) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2537).

References

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