organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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3,3,12,12-Tetra­methyl-1,5,10,14-tetra­oxa­di­spiro­[5.2.5.2]hexa­deca­ne

aJiangsu Institute of Nuclear Medicine, Wuxi 214063, People's Republic of China
*Correspondence e-mail: yongjunhe001@hotmail.com

(Received 18 May 2009; accepted 4 June 2009; online 13 June 2009)

The mol­ecule of the title compound, C16H28O4, is centrosymmetric. The cyclo­hexane ring and both six-membered dioxane rings adopt chair conformations. In the crystal, the mol­ecules lie in layers in the (100) planes and the shortest inter­molecular contacts are H⋯H (2.30 Å).

Related literature

The title compound is an inter­mediate in the synthesis of Frovatriptan, a 5-HT1-like agonist, see: Borrett et al. (1999[Borrett, G. T., Kitteringham, J., Porter, R. A., Shipton, M. R., Vimal, M. & Young, R. C. (1999). US Patent No. 5 962 501.]). For details of the synthesis, see: Babler & Spina (1984[Babler, J. H. & Spina, K. P. (1984). Synth. Commun. 14, 39-44.]); Borrett et al. (1999[Borrett, G. T., Kitteringham, J., Porter, R. A., Shipton, M. R., Vimal, M. & Young, R. C. (1999). US Patent No. 5 962 501.]). For a related structure, see: Luger et al. (1972[Luger, P., Plieth, K. & Ruban, G. (1972). Acta Cryst. B28, 706-710.]).

[Scheme 1]

Experimental

Crystal data
  • C16H28O4

  • Mr = 284.38

  • Monoclinic, P 21 /c

  • a = 12.639 (8) Å

  • b = 5.838 (4) Å

  • c = 11.179 (7) Å

  • β = 110.611 (8)°

  • V = 772.1 (9) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 93 K

  • 0.43 × 0.37 × 0.14 mm

Data collection
  • Rigaku SPIDER diffractometer

  • Absorption correction: none

  • 5721 measured reflections

  • 1752 independent reflections

  • 1243 reflections with I > 2σ(I)

  • Rint = 0.048

Refinement
  • R[F2 > 2σ(F2)] = 0.049

  • wR(F2) = 0.095

  • S = 1.00

  • 1752 reflections

  • 93 parameters

  • H-atom parameters constrained

  • Δρmax = 0.27 e Å−3

  • Δρmin = −0.19 e Å−3

Data collection: RAPID-AUTO (Rigaku 2004[Rigaku (2004). RAPID-AUTO. Rigaku Corporation, Tokyo, Japan.]); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

The title compound is useful as an intermediate in the synthesis of Frovatriptan, a 5-HT1-like agonist (Babler & Spina, 1984; Borrett et al., 1999). The molecular structure is shown in Fig. 1. Three six-membered rings exhibit chair conformations, with C—C bond lengths in the range 1.516 (2)–1.527 (2) Å and C—C—C angles in the range 106.59 (13)–112.55 (13)°; these agree well with the values in other cyclohexane derivatives described in the literature (Luger et al., 1972).

Related literature top

The title compound is an intermediate in the synthesis of Frovatriptan, a 5-HT1-like agonist, see: Borrett et al. (1999). For details of the synthesis, see: Babler & Spina (1984); Borrett et al. (1999). For a related structure, see: Luger et al. (1972).

Experimental top

The title compound was obtained by reaction of 1,4-cyclohexanedione (20 mmol), 2,2-dimethyl-1,3-propanediol (40 mmol) and sulfuric acid (0.1 mmol) in hexane (20 ml). The mixture was stirred for 6 h at 333 K. Colourless block-shaped crystals suitable for X-ray diffraction analysis were grown at the bottom of the vessel after 7 days slow evaporation of the solution at room temperature.

Refinement top

H atoms were placed in calculated positions with C—H = 0.99 and 0.98 Å for methylene and methyl H atoms, respectively, and refined as riding with Uiso(H) = 1.2 or 1.5Ueq(C).

Computing details top

Data collection: RAPID-AUTO (Rigaku 2004); cell refinement: RAPID-AUTO (Rigaku 2004); data reduction: RAPID-AUTO (Rigaku 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure with displacement ellipsoids drawn at the 30% probability level for non-H atoms. Non-labelled atoms are related to labelled atoms by the symmetry operator: 1 - x, 1 - y, 1 - z.
3,3,12,12-Tetramethyl-1,5,10,14-tetraoxadispiro[5.2.5.2]hexadecane top
Crystal data top
C16H28O4F(000) = 312
Mr = 284.38Dx = 1.223 Mg m3
Monoclinic, P21/cMelting point: 430 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 12.639 (8) ÅCell parameters from 2071 reflections
b = 5.838 (4) Åθ = 3.3–27.5°
c = 11.179 (7) ŵ = 0.09 mm1
β = 110.611 (8)°T = 93 K
V = 772.1 (9) Å3Block, colourless
Z = 20.43 × 0.37 × 0.14 mm
Data collection top
Rigaku SPIDER
diffractometer
1243 reflections with I > 2σ(I)
Radiation source: Rotating AnodeRint = 0.048
Graphite monochromatorθmax = 27.5°, θmin = 3.4°
ω scansh = 1616
5721 measured reflectionsk = 77
1752 independent reflectionsl = 1314
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.095H-atom parameters constrained
S = 1.00 w = 1/[σ2(Fo2) + (0.0116P)2 + 0.36P]
where P = (Fo2 + 2Fc2)/3
1752 reflections(Δ/σ)max < 0.001
93 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = 0.19 e Å3
Crystal data top
C16H28O4V = 772.1 (9) Å3
Mr = 284.38Z = 2
Monoclinic, P21/cMo Kα radiation
a = 12.639 (8) ŵ = 0.09 mm1
b = 5.838 (4) ÅT = 93 K
c = 11.179 (7) Å0.43 × 0.37 × 0.14 mm
β = 110.611 (8)°
Data collection top
Rigaku SPIDER
diffractometer
1243 reflections with I > 2σ(I)
5721 measured reflectionsRint = 0.048
1752 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0490 restraints
wR(F2) = 0.095H-atom parameters constrained
S = 1.00Δρmax = 0.27 e Å3
1752 reflectionsΔρmin = 0.19 e Å3
93 parameters
Special details top

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) top
xyzUiso*/Ueq
O10.68024 (9)0.62454 (18)0.57453 (10)0.0219 (3)
O20.66546 (9)0.37232 (18)0.73088 (10)0.0221 (3)
C10.43232 (13)0.7060 (3)0.48564 (15)0.0224 (4)
H1A0.36490.78510.49120.027*
H1B0.47680.81940.45740.027*
C20.50381 (13)0.6171 (3)0.61780 (15)0.0220 (4)
H2A0.52990.74780.67740.026*
H2B0.45700.51660.65050.026*
C30.60572 (13)0.4836 (3)0.61294 (15)0.0204 (4)
C40.74097 (14)0.7887 (3)0.66956 (15)0.0232 (4)
H4A0.68680.89770.68430.028*
H4B0.79280.87680.63800.028*
C50.80864 (13)0.6730 (3)0.79466 (15)0.0217 (4)
C60.72591 (14)0.5256 (3)0.83191 (15)0.0222 (4)
H6A0.76770.43600.90930.027*
H6B0.67150.62570.85260.027*
C70.85930 (15)0.8559 (3)0.89653 (16)0.0284 (4)
H7A0.90830.95710.86910.034*
H7B0.90380.78200.97730.034*
H7C0.79830.94590.90850.034*
C80.90174 (14)0.5242 (3)0.77798 (16)0.0288 (4)
H8A0.86800.40970.71130.035*
H8B0.94300.44660.85870.035*
H8C0.95410.62060.75320.035*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0275 (6)0.0188 (6)0.0206 (6)0.0030 (5)0.0099 (5)0.0001 (5)
O20.0292 (6)0.0154 (6)0.0197 (6)0.0016 (5)0.0060 (5)0.0013 (5)
C10.0282 (9)0.0151 (8)0.0240 (9)0.0018 (6)0.0093 (7)0.0016 (7)
C20.0262 (9)0.0184 (8)0.0217 (9)0.0008 (6)0.0087 (7)0.0019 (7)
C30.0254 (9)0.0167 (8)0.0188 (8)0.0007 (6)0.0074 (7)0.0024 (7)
C40.0289 (9)0.0160 (8)0.0240 (9)0.0042 (7)0.0083 (7)0.0000 (7)
C50.0258 (9)0.0182 (8)0.0209 (9)0.0010 (7)0.0083 (7)0.0002 (7)
C60.0277 (9)0.0207 (8)0.0175 (9)0.0002 (7)0.0073 (7)0.0003 (7)
C70.0331 (10)0.0254 (9)0.0253 (10)0.0041 (8)0.0084 (8)0.0010 (8)
C80.0281 (9)0.0291 (10)0.0293 (10)0.0016 (7)0.0105 (8)0.0008 (8)
Geometric parameters (Å, º) top
O1—C31.4258 (19)C4—H4A0.990
O1—C41.4362 (19)C4—H4B0.990
O2—C31.4248 (19)C5—C61.521 (2)
O2—C61.4328 (19)C5—C81.526 (2)
C1—C3i1.516 (2)C5—C71.527 (2)
C1—C21.526 (2)C6—H6A0.990
C1—H1A0.990C6—H6B0.990
C1—H1B0.990C7—H7A0.980
C2—C31.523 (2)C7—H7B0.980
C2—H2A0.990C7—H7C0.980
C2—H2B0.990C8—H8A0.980
C3—C1i1.516 (2)C8—H8B0.980
C4—C51.517 (2)C8—H8C0.980
C3—O1—C4113.58 (12)H4A—C4—H4B108.0
C3—O2—C6113.98 (12)C4—C5—C6106.59 (13)
C3i—C1—C2112.55 (13)C4—C5—C8110.46 (14)
C3i—C1—H1A109.1C6—C5—C8110.18 (14)
C2—C1—H1A109.1C4—C5—C7109.17 (14)
C3i—C1—H1B109.1C6—C5—C7109.84 (14)
C2—C1—H1B109.1C8—C5—C7110.50 (14)
H1A—C1—H1B107.8O2—C6—C5111.39 (13)
C3—C2—C1111.07 (13)O2—C6—H6A109.3
C3—C2—H2A109.4C5—C6—H6A109.3
C1—C2—H2A109.4O2—C6—H6B109.3
C3—C2—H2B109.4C5—C6—H6B109.3
C1—C2—H2B109.4H6A—C6—H6B108.0
H2A—C2—H2B108.0C5—C7—H7A109.5
O2—C3—O1110.54 (12)C5—C7—H7B109.5
O2—C3—C1i105.59 (13)H7A—C7—H7B109.5
O1—C3—C1i106.05 (13)C5—C7—H7C109.5
O2—C3—C2112.32 (13)H7A—C7—H7C109.5
O1—C3—C2111.86 (13)H7B—C7—H7C109.5
C1i—C3—C2110.12 (13)C5—C8—H8A109.5
O1—C4—C5111.45 (13)C5—C8—H8B109.5
O1—C4—H4A109.3H8A—C8—H8B109.5
C5—C4—H4A109.3C5—C8—H8C109.5
O1—C4—H4B109.3H8A—C8—H8C109.5
C5—C4—H4B109.3H8B—C8—H8C109.5
C3i—C1—C2—C356.01 (19)C1—C2—C3—C1i54.63 (18)
C6—O2—C3—O154.99 (16)C3—O1—C4—C557.12 (17)
C6—O2—C3—C1i169.25 (12)O1—C4—C5—C654.38 (17)
C6—O2—C3—C270.72 (16)O1—C4—C5—C865.32 (17)
C4—O1—C3—O255.06 (16)O1—C4—C5—C7172.97 (13)
C4—O1—C3—C1i169.04 (12)C3—O2—C6—C556.61 (17)
C4—O1—C3—C270.90 (16)C4—C5—C6—O254.05 (17)
C1—C2—C3—O2172.00 (12)C8—C5—C6—O265.83 (17)
C1—C2—C3—O163.02 (16)C7—C5—C6—O2172.21 (13)
Symmetry code: (i) x+1, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC16H28O4
Mr284.38
Crystal system, space groupMonoclinic, P21/c
Temperature (K)93
a, b, c (Å)12.639 (8), 5.838 (4), 11.179 (7)
β (°) 110.611 (8)
V3)772.1 (9)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.43 × 0.37 × 0.14
Data collection
DiffractometerRigaku SPIDER
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5721, 1752, 1243
Rint0.048
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.095, 1.00
No. of reflections1752
No. of parameters93
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.27, 0.19

Computer programs: RAPID-AUTO (Rigaku 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

The authors acknowledge financial support from Jiangsu Institute of Nuclear Medicine.

References

First citationBabler, J. H. & Spina, K. P. (1984). Synth. Commun. 14, 39–44.  CrossRef CAS Web of Science Google Scholar
First citationBorrett, G. T., Kitteringham, J., Porter, R. A., Shipton, M. R., Vimal, M. & Young, R. C. (1999). US Patent No. 5 962 501.  Google Scholar
First citationLuger, P., Plieth, K. & Ruban, G. (1972). Acta Cryst. B28, 706–710.  CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
First citationRigaku (2004). RAPID-AUTO. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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ISSN: 2056-9890
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