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

He, Y.-J.; Xie, M.-H.; Zou, P.; Liu, Y.-L.; Wu, J.

doi:10.1107/S1600536809021291

organic compounds

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ISSN: 2056-9890

Volume 65| Part 7| July 2009| Page o1559

doi:10.1107/S1600536809021291

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

Yong-Jun He,^a Min-Hao Xie,^a ^* Pei Zou,^a Ya-Ling Liu ^a and Jun Wu ^a

^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 ). For details of the synthesis, see: Babler & Spina (1984 ); Borrett et al. (1999). For a related structure, see: Luger et al. (1972 ).

Experimental

Crystal data

C₁₆H₂₈O₄
M_r = 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)
R_int = 0.048

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.095
S = 1.00
1752 reflections
93 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: RAPID-AUTO (Rigaku 2004 ); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809021291/bi2376sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809021291/bi2376Isup2.hkl

checkCIF report

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.

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

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

C₁₆H₂₈O₄	F(000) = 312
M_r = 284.38	D_x = 1.223 Mg m⁻³
Monoclinic, P2₁/c	Melting point: 430 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 12.639 (8) Å	Cell parameters from 2071 reflections
b = 5.838 (4) Å	θ = 3.3–27.5°
c = 11.179 (7) Å	µ = 0.09 mm⁻¹
β = 110.611 (8)°	T = 93 K
V = 772.1 (9) Å³	Block, colourless
Z = 2	0.43 × 0.37 × 0.14 mm

Data collection top

Rigaku SPIDER diffractometer	1243 reflections with I > 2σ(I)
Radiation source: Rotating Anode	R_int = 0.048
Graphite monochromator	θ_max = 27.5°, θ_min = 3.4°
ω scans	h = −16→16
5721 measured reflections	k = −7→7
1752 independent reflections	l = −13→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.095	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0116P)² + 0.36P] where P = (F_o² + 2F_c²)/3
1752 reflections	(Δ/σ)_max < 0.001
93 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³

Crystal data top

C₁₆H₂₈O₄	V = 772.1 (9) Å³
M_r = 284.38	Z = 2
Monoclinic, P2₁/c	Mo Kα radiation
a = 12.639 (8) Å	µ = 0.09 mm⁻¹
b = 5.838 (4) Å	T = 93 K
c = 11.179 (7) Å	0.43 × 0.37 × 0.14 mm
β = 110.611 (8)°

Data collection top

Rigaku SPIDER diffractometer	1243 reflections with I > 2σ(I)
5721 measured reflections	R_int = 0.048
1752 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.095	H-atom parameters constrained
S = 1.00	Δρ_max = 0.27 e Å⁻³
1752 reflections	Δρ_min = −0.19 e Å⁻³
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

	x	y	z	U_iso*/U_eq
O1	0.68024 (9)	0.62454 (18)	0.57453 (10)	0.0219 (3)
O2	0.66546 (9)	0.37232 (18)	0.73088 (10)	0.0221 (3)
C1	0.43232 (13)	0.7060 (3)	0.48564 (15)	0.0224 (4)
H1A	0.3649	0.7851	0.4912	0.027*
H1B	0.4768	0.8194	0.4574	0.027*
C2	0.50381 (13)	0.6171 (3)	0.61780 (15)	0.0220 (4)
H2A	0.5299	0.7478	0.6774	0.026*
H2B	0.4570	0.5166	0.6505	0.026*
C3	0.60572 (13)	0.4836 (3)	0.61294 (15)	0.0204 (4)
C4	0.74097 (14)	0.7887 (3)	0.66956 (15)	0.0232 (4)
H4A	0.6868	0.8977	0.6843	0.028*
H4B	0.7928	0.8768	0.6380	0.028*
C5	0.80864 (13)	0.6730 (3)	0.79466 (15)	0.0217 (4)
C6	0.72591 (14)	0.5256 (3)	0.83191 (15)	0.0222 (4)
H6A	0.7677	0.4360	0.9093	0.027*
H6B	0.6715	0.6257	0.8526	0.027*
C7	0.85930 (15)	0.8559 (3)	0.89653 (16)	0.0284 (4)
H7A	0.9083	0.9571	0.8691	0.034*
H7B	0.9038	0.7820	0.9773	0.034*
H7C	0.7983	0.9459	0.9085	0.034*
C8	0.90174 (14)	0.5242 (3)	0.77798 (16)	0.0288 (4)
H8A	0.8680	0.4097	0.7113	0.035*
H8B	0.9430	0.4466	0.8587	0.035*
H8C	0.9541	0.6206	0.7532	0.035*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0275 (6)	0.0188 (6)	0.0206 (6)	−0.0030 (5)	0.0099 (5)	−0.0001 (5)
O2	0.0292 (6)	0.0154 (6)	0.0197 (6)	−0.0016 (5)	0.0060 (5)	0.0013 (5)
C1	0.0282 (9)	0.0151 (8)	0.0240 (9)	0.0018 (6)	0.0093 (7)	−0.0016 (7)
C2	0.0262 (9)	0.0184 (8)	0.0217 (9)	0.0008 (6)	0.0087 (7)	−0.0019 (7)
C3	0.0254 (9)	0.0167 (8)	0.0188 (8)	−0.0007 (6)	0.0074 (7)	0.0024 (7)
C4	0.0289 (9)	0.0160 (8)	0.0240 (9)	−0.0042 (7)	0.0083 (7)	0.0000 (7)
C5	0.0258 (9)	0.0182 (8)	0.0209 (9)	−0.0010 (7)	0.0083 (7)	0.0002 (7)
C6	0.0277 (9)	0.0207 (8)	0.0175 (9)	0.0002 (7)	0.0073 (7)	0.0003 (7)
C7	0.0331 (10)	0.0254 (9)	0.0253 (10)	−0.0041 (8)	0.0084 (8)	−0.0010 (8)
C8	0.0281 (9)	0.0291 (10)	0.0293 (10)	0.0016 (7)	0.0105 (8)	0.0008 (8)

Geometric parameters (Å, º) top

O1—C3	1.4258 (19)	C4—H4A	0.990
O1—C4	1.4362 (19)	C4—H4B	0.990
O2—C3	1.4248 (19)	C5—C6	1.521 (2)
O2—C6	1.4328 (19)	C5—C8	1.526 (2)
C1—C3ⁱ	1.516 (2)	C5—C7	1.527 (2)
C1—C2	1.526 (2)	C6—H6A	0.990
C1—H1A	0.990	C6—H6B	0.990
C1—H1B	0.990	C7—H7A	0.980
C2—C3	1.523 (2)	C7—H7B	0.980
C2—H2A	0.990	C7—H7C	0.980
C2—H2B	0.990	C8—H8A	0.980
C3—C1ⁱ	1.516 (2)	C8—H8B	0.980
C4—C5	1.517 (2)	C8—H8C	0.980

C3—O1—C4	113.58 (12)	H4A—C4—H4B	108.0
C3—O2—C6	113.98 (12)	C4—C5—C6	106.59 (13)
C3ⁱ—C1—C2	112.55 (13)	C4—C5—C8	110.46 (14)
C3ⁱ—C1—H1A	109.1	C6—C5—C8	110.18 (14)
C2—C1—H1A	109.1	C4—C5—C7	109.17 (14)
C3ⁱ—C1—H1B	109.1	C6—C5—C7	109.84 (14)
C2—C1—H1B	109.1	C8—C5—C7	110.50 (14)
H1A—C1—H1B	107.8	O2—C6—C5	111.39 (13)
C3—C2—C1	111.07 (13)	O2—C6—H6A	109.3
C3—C2—H2A	109.4	C5—C6—H6A	109.3
C1—C2—H2A	109.4	O2—C6—H6B	109.3
C3—C2—H2B	109.4	C5—C6—H6B	109.3
C1—C2—H2B	109.4	H6A—C6—H6B	108.0
H2A—C2—H2B	108.0	C5—C7—H7A	109.5
O2—C3—O1	110.54 (12)	C5—C7—H7B	109.5
O2—C3—C1ⁱ	105.59 (13)	H7A—C7—H7B	109.5
O1—C3—C1ⁱ	106.05 (13)	C5—C7—H7C	109.5
O2—C3—C2	112.32 (13)	H7A—C7—H7C	109.5
O1—C3—C2	111.86 (13)	H7B—C7—H7C	109.5
C1ⁱ—C3—C2	110.12 (13)	C5—C8—H8A	109.5
O1—C4—C5	111.45 (13)	C5—C8—H8B	109.5
O1—C4—H4A	109.3	H8A—C8—H8B	109.5
C5—C4—H4A	109.3	C5—C8—H8C	109.5
O1—C4—H4B	109.3	H8A—C8—H8C	109.5
C5—C4—H4B	109.3	H8B—C8—H8C	109.5

C3ⁱ—C1—C2—C3	56.01 (19)	C1—C2—C3—C1ⁱ	−54.63 (18)
C6—O2—C3—O1	54.99 (16)	C3—O1—C4—C5	57.12 (17)
C6—O2—C3—C1ⁱ	169.25 (12)	O1—C4—C5—C6	−54.38 (17)
C6—O2—C3—C2	−70.72 (16)	O1—C4—C5—C8	65.32 (17)
C4—O1—C3—O2	−55.06 (16)	O1—C4—C5—C7	−172.97 (13)
C4—O1—C3—C1ⁱ	−169.04 (12)	C3—O2—C6—C5	−56.61 (17)
C4—O1—C3—C2	70.90 (16)	C4—C5—C6—O2	54.05 (17)
C1—C2—C3—O2	−172.00 (12)	C8—C5—C6—O2	−65.83 (17)
C1—C2—C3—O1	63.02 (16)	C7—C5—C6—O2	172.21 (13)

Symmetry code: (i) −x+1, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₆H₂₈O₄
M_r	284.38
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	93
a, b, c (Å)	12.639 (8), 5.838 (4), 11.179 (7)
β (°)	110.611 (8)
V (Å³)	772.1 (9)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.43 × 0.37 × 0.14

Data collection
Diffractometer	Rigaku SPIDER diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5721, 1752, 1243
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.095, 1.00
No. of reflections	1752
No. of parameters	93
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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

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