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

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ISSN: 2056-9890

(4-Ethyl­cyclo­hex­yl)(4-meth­­oxy­phen­yl)methanone

aPharmacy Department of the Second Artillery General Hospital, Beijing 100088, People's Republic of China, and bMedical Material Purchasing Center of PLA General Hospital, Beijing 100088, People's Republic of China
*Correspondence e-mail: chunlei.ding@yahoo.com

(Received 30 January 2013; accepted 31 January 2013; online 6 February 2013)

In the title compound, C16H22O2, the cyclo­hexane ring adopts a chair conformation and its mean plane subtends a dihedral angle of 54.2 (6)° with the benzene ring. The crystal structure is stabilized by van der Waals inter­actions only with no classical inter­molecular hydrogen bonding observed.

Related literature

For details of SGLT2 inhibitors, a new class of hypoglycemic agents, see: Washburn (2009[Washburn, W. N. (2009). J. Med. Chem. 52, 1785-1794.]); Zhao et al. (2011[Zhao, W. J., Shi, Y. H., Zhao, G. L., Wang, Y. L., Shao, H., Tang, L. D. & Wang, J. W. (2011). Chin. Chem. Lett. 22, 1215-1218.]); Shao et al. (2011[Shao, H., Gao, Y. L., Lou, Y. Y., Wang, Y. L., Liu, W., Xu, W. R., Wang, J. W., Zhao, G. L. & Tang, L. D. (2011). Chin. J. Org. Chem. 31, 836-842.]). For the crystal structures of cyclo­hexyl derivertives, see: Wang et al. (2011[Wang, L., Chang, Z., Ding, C., Shao, H. & Sun, J. (2011). Acta Cryst. E67, o1173.]).

[Scheme 1]

Experimental

Crystal data
  • C16H22O2

  • Mr = 246.34

  • Monoclinic, P 21 /c

  • a = 7.613 (2) Å

  • b = 5.7513 (15) Å

  • c = 31.085 (9) Å

  • β = 94.674 (4)°

  • V = 1356.5 (6) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 113 K

  • 0.20 × 0.18 × 0.10 mm

Data collection
  • Rigaku Saturn CCD area-detector diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2009)[Rigaku/MSC (2009). CrystalClear-SM Expert and CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.] Tmin = 0.985, Tmax = 0.992

  • 13145 measured reflections

  • 3235 independent reflections

  • 2576 reflections with I > 2σ(I)

  • Rint = 0.042

Refinement
  • R[F2 > 2σ(F2)] = 0.050

  • wR(F2) = 0.139

  • S = 1.06

  • 3235 reflections

  • 165 parameters

  • H-atom parameters constrained

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.18 e Å−3

Data collection: CrystalClear-SM Expert (Rigaku/MSC, 2009)[Rigaku/MSC (2009). CrystalClear-SM Expert and CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.]; cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; 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

SGLT2 inhibitors are a new class of hypoglycemic agents, and the most advanced drug dapagliflozin has been approved recently in EU for the treatment of type 2 diabetes (Washburn, 2009). During the study on the SGLT2 inhibitors in our laboratory, the title compound was prepared which is a key intermediate for the synthetic procedure (Zhao et al., 2011; Shao et al., 2011).

In the title compound, C16H22O2, bond lengths are normal and and in good agreement with those reported previously (Wang et al., 2011). The cyclohexane ring adopts a chair conformation and its least squares plane (C10/C11/C13/C14) is at an angle of 54.2 (6)° to the benzene ring (C2—C7). The crystal structure is stabilized by van der Waals interactions only with no classical inter-molecular hydrogen bonding observed.

Related literature top

For details of SGLT2 inhibitors, a new class of hypoglycemic agents, see: Washburn (2009); Zhao et al. (2011); Shao et al. (2011). For the crystal structures of cyclohexyl derivertives, see: Wang et al. (2011).

Experimental top

15.62 g (0.1 mol) of trans-4-ethylcyclohexanecarboxylic acid was stirred in 150 ml of dried CH2Cl2 at room temperature. 17.80 g (0.13 mol) of freshly distilled oxalyl chloride was added dropwise followed by addition of 0.1 ml of dried DMF. The mixture was stirred at room temperature for 5 h and evaporated in vacuo to give a residue. The residue was dissolved in 80 ml of dried dichloromethane followed by addition of 10.81 g (0.1 mol) of anisole. The mixture thus obtained was stirred at 0oC followed by portionwise addition of 14.67 g (0.11 mol) of AlCl3. The reaction mixture was then stirred at room temperature overnight, poured into 300 ml of ice-water and extracted with 100 ml three times of dichloromethane. The combined extracts were washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by column chromatography to afford the pure title compound as colorless crystals. The single crystals suitable for single-crystal X-ray diffraction were obtained by slow evaporation at room temperature of a 0.2 M solution of the title compound in dichloromethane/hexane (1/12 by v/v).

Refinement top

All H atoms bonded on carbon were found on difference maps, with C–H = 0.95–1.00, and included in the final cycles of refinement using a riding model, with Uiso(H) = 1.2Ueq(C) and 1.5Ueq(C) for the methyl H atoms.

Computing details top

Data collection: CrystalClear-SM Expert (Rigaku/MSC, 2009); cell refinement: CrystalClear-SM Expert (Rigaku/MSC, 2009); data reduction: CrystalClear-SM Expert (Rigaku/MSC, 2009); 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. View of the title compound showing the atomic numbering and 40% probability displacement ellipsoids.
(4-Ethylcyclohexyl)(4-methoxyphenyl)methanone top
Crystal data top
C16H22O2F(000) = 536
Mr = 246.34Dx = 1.206 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3595 reflections
a = 7.613 (2) Åθ = 1.3–27.9°
b = 5.7513 (15) ŵ = 0.08 mm1
c = 31.085 (9) ÅT = 113 K
β = 94.674 (4)°Prism, colorless
V = 1356.5 (6) Å30.20 × 0.18 × 0.10 mm
Z = 4
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
3235 independent reflections
Radiation source: rotating anode2576 reflections with I > 2σ(I)
Multilayer monochromatorRint = 0.042
Detector resolution: 14.63 pixels mm-1θmax = 27.9°, θmin = 1.3°
ω and ϕ scansh = 910
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2009)
k = 67
Tmin = 0.985, Tmax = 0.992l = 4040
13145 measured reflections
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)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.139H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0684P)2 + 0.0117P]
where P = (Fo2 + 2Fc2)/3
3235 reflections(Δ/σ)max = 0.001
165 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = 0.18 e Å3
Crystal data top
C16H22O2V = 1356.5 (6) Å3
Mr = 246.34Z = 4
Monoclinic, P21/cMo Kα radiation
a = 7.613 (2) ŵ = 0.08 mm1
b = 5.7513 (15) ÅT = 113 K
c = 31.085 (9) Å0.20 × 0.18 × 0.10 mm
β = 94.674 (4)°
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
3235 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2009)
2576 reflections with I > 2σ(I)
Tmin = 0.985, Tmax = 0.992Rint = 0.042
13145 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0500 restraints
wR(F2) = 0.139H-atom parameters constrained
S = 1.06Δρmax = 0.25 e Å3
3235 reflectionsΔρmin = 0.18 e Å3
165 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
O10.34006 (12)0.74119 (17)0.16856 (3)0.0272 (3)
O20.05937 (15)0.53751 (18)0.34949 (3)0.0352 (3)
C10.3969 (2)0.9518 (3)0.14967 (4)0.0316 (4)
H1A0.31071.07500.15360.047*
H1B0.40730.92760.11880.047*
H1C0.51170.99740.16370.047*
C20.29562 (17)0.7517 (2)0.21018 (4)0.0215 (3)
C30.20950 (17)0.5560 (2)0.22446 (4)0.0229 (3)
H30.18690.42730.20570.028*
C40.15706 (17)0.5488 (2)0.26592 (4)0.0212 (3)
H40.09860.41470.27550.025*
C50.18896 (17)0.7370 (2)0.29413 (4)0.0198 (3)
C60.27745 (17)0.9302 (2)0.27951 (4)0.0215 (3)
H60.30131.05820.29840.026*
C70.33165 (18)0.9393 (2)0.23779 (4)0.0215 (3)
H70.39231.07180.22830.026*
C80.12147 (18)0.7220 (2)0.33787 (4)0.0229 (3)
C90.13144 (17)0.9305 (2)0.36774 (4)0.0213 (3)
H90.11511.07480.34990.026*
C100.01352 (18)0.9211 (2)0.39925 (4)0.0245 (3)
H10A0.13030.92920.38280.029*
H10B0.00610.77140.41500.029*
C110.00388 (17)1.1215 (2)0.43170 (4)0.0239 (3)
H11A0.08901.10690.45210.029*
H11B0.01441.27080.41610.029*
C120.18477 (18)1.1241 (2)0.45716 (4)0.0219 (3)
H120.20010.97300.47300.026*
C130.32707 (18)1.1398 (2)0.42528 (4)0.0235 (3)
H13A0.44461.13780.44140.028*
H13B0.31471.28920.40950.028*
C140.31498 (18)0.9391 (2)0.39280 (4)0.0233 (3)
H14A0.33760.79030.40830.028*
H14B0.40640.95880.37220.028*
C150.19885 (19)1.3203 (3)0.49047 (4)0.0264 (3)
H15A0.20861.47000.47510.032*
H15B0.08861.32480.50530.032*
C160.3545 (2)1.2989 (3)0.52446 (4)0.0319 (4)
H16A0.33851.16160.54240.048*
H16B0.36091.43830.54270.048*
H16C0.46391.28320.51010.048*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0309 (6)0.0321 (6)0.0196 (5)0.0005 (4)0.0068 (4)0.0025 (4)
O20.0550 (7)0.0257 (6)0.0261 (6)0.0095 (5)0.0099 (5)0.0028 (4)
C10.0357 (9)0.0380 (10)0.0223 (7)0.0010 (7)0.0089 (6)0.0029 (6)
C20.0185 (7)0.0272 (8)0.0186 (6)0.0026 (6)0.0004 (5)0.0004 (5)
C30.0230 (7)0.0221 (8)0.0234 (7)0.0009 (6)0.0000 (5)0.0032 (5)
C40.0197 (7)0.0188 (7)0.0247 (7)0.0007 (5)0.0008 (5)0.0022 (5)
C50.0200 (7)0.0209 (7)0.0180 (6)0.0014 (5)0.0012 (5)0.0012 (5)
C60.0231 (7)0.0220 (8)0.0188 (7)0.0000 (6)0.0010 (5)0.0005 (5)
C70.0212 (7)0.0216 (8)0.0218 (7)0.0007 (5)0.0018 (5)0.0016 (5)
C80.0233 (7)0.0232 (8)0.0216 (7)0.0001 (6)0.0008 (5)0.0038 (5)
C90.0252 (8)0.0221 (8)0.0167 (6)0.0005 (6)0.0022 (5)0.0025 (5)
C100.0237 (8)0.0296 (8)0.0203 (7)0.0025 (6)0.0021 (5)0.0020 (5)
C110.0224 (7)0.0300 (8)0.0198 (6)0.0019 (6)0.0057 (5)0.0019 (5)
C120.0251 (7)0.0233 (8)0.0177 (6)0.0006 (6)0.0034 (5)0.0015 (5)
C130.0229 (7)0.0257 (8)0.0221 (7)0.0018 (6)0.0026 (5)0.0001 (5)
C140.0230 (7)0.0267 (8)0.0207 (7)0.0005 (6)0.0043 (5)0.0007 (5)
C150.0316 (8)0.0260 (8)0.0221 (7)0.0012 (6)0.0043 (6)0.0015 (5)
C160.0367 (9)0.0360 (9)0.0230 (7)0.0035 (7)0.0025 (6)0.0045 (6)
Geometric parameters (Å, º) top
O1—C21.3649 (15)C10—C111.5302 (18)
O1—C11.4286 (16)C10—H10A0.9900
O2—C81.2281 (16)C10—H10B0.9900
C1—H1A0.9800C11—C121.5313 (18)
C1—H1B0.9800C11—H11A0.9900
C1—H1C0.9800C11—H11B0.9900
C2—C71.3923 (18)C12—C131.5294 (18)
C2—C31.3933 (19)C12—C151.5295 (18)
C3—C41.3805 (18)C12—H121.0000
C3—H30.9500C13—C141.5315 (18)
C4—C51.4017 (18)C13—H13A0.9900
C4—H40.9500C13—H13B0.9900
C5—C61.3941 (18)C14—H14A0.9900
C5—C81.4946 (18)C14—H14B0.9900
C6—C71.3935 (17)C15—C161.5269 (19)
C6—H60.9500C15—H15A0.9900
C7—H70.9500C15—H15B0.9900
C8—C91.5146 (18)C16—H16A0.9800
C9—C101.5352 (18)C16—H16B0.9800
C9—C141.5441 (18)C16—H16C0.9800
C9—H91.0000
C2—O1—C1117.31 (11)C9—C10—H10B109.3
O1—C1—H1A109.5H10A—C10—H10B108.0
O1—C1—H1B109.5C10—C11—C12111.94 (11)
H1A—C1—H1B109.5C10—C11—H11A109.2
O1—C1—H1C109.5C12—C11—H11A109.2
H1A—C1—H1C109.5C10—C11—H11B109.2
H1B—C1—H1C109.5C12—C11—H11B109.2
O1—C2—C7124.55 (12)H11A—C11—H11B107.9
O1—C2—C3115.20 (12)C13—C12—C15112.37 (11)
C7—C2—C3120.25 (12)C13—C12—C11108.69 (11)
C4—C3—C2120.06 (12)C15—C12—C11111.55 (11)
C4—C3—H3120.0C13—C12—H12108.0
C2—C3—H3120.0C15—C12—H12108.0
C3—C4—C5120.83 (13)C11—C12—H12108.0
C3—C4—H4119.6C12—C13—C14112.00 (11)
C5—C4—H4119.6C12—C13—H13A109.2
C6—C5—C4118.36 (12)C14—C13—H13A109.2
C6—C5—C8123.61 (12)C12—C13—H13B109.2
C4—C5—C8118.01 (12)C14—C13—H13B109.2
C7—C6—C5121.40 (12)H13A—C13—H13B107.9
C7—C6—H6119.3C13—C14—C9111.10 (11)
C5—C6—H6119.3C13—C14—H14A109.4
C2—C7—C6119.08 (12)C9—C14—H14A109.4
C2—C7—H7120.5C13—C14—H14B109.4
C6—C7—H7120.5C9—C14—H14B109.4
O2—C8—C5119.12 (12)H14A—C14—H14B108.0
O2—C8—C9120.34 (12)C16—C15—C12114.64 (12)
C5—C8—C9120.54 (12)C16—C15—H15A108.6
C8—C9—C10111.14 (11)C12—C15—H15A108.6
C8—C9—C14109.43 (11)C16—C15—H15B108.6
C10—C9—C14110.31 (11)C12—C15—H15B108.6
C8—C9—H9108.6H15A—C15—H15B107.6
C10—C9—H9108.6C15—C16—H16A109.5
C14—C9—H9108.6C15—C16—H16B109.5
C11—C10—C9111.47 (11)H16A—C16—H16B109.5
C11—C10—H10A109.3C15—C16—H16C109.5
C9—C10—H10A109.3H16A—C16—H16C109.5
C11—C10—H10B109.3H16B—C16—H16C109.5
C1—O1—C2—C712.28 (19)O2—C8—C9—C1027.46 (17)
C1—O1—C2—C3168.14 (11)C5—C8—C9—C10153.29 (12)
O1—C2—C3—C4179.40 (11)O2—C8—C9—C1494.61 (15)
C7—C2—C3—C41.0 (2)C5—C8—C9—C1484.64 (14)
C2—C3—C4—C50.1 (2)C8—C9—C10—C11175.81 (10)
C3—C4—C5—C61.00 (19)C14—C9—C10—C1154.25 (14)
C3—C4—C5—C8177.29 (12)C9—C10—C11—C1256.99 (14)
C4—C5—C6—C70.78 (19)C10—C11—C12—C1357.33 (14)
C8—C5—C6—C7177.40 (12)C10—C11—C12—C15178.23 (11)
O1—C2—C7—C6179.23 (12)C15—C12—C13—C14178.48 (10)
C3—C2—C7—C61.21 (19)C11—C12—C13—C1457.57 (14)
C5—C6—C7—C20.3 (2)C12—C13—C14—C957.13 (15)
C6—C5—C8—O2173.42 (12)C8—C9—C14—C13176.81 (11)
C4—C5—C8—O28.38 (19)C10—C9—C14—C1354.24 (14)
C6—C5—C8—C95.83 (19)C13—C12—C15—C1672.27 (15)
C4—C5—C8—C9172.36 (12)C11—C12—C15—C16165.39 (12)

Experimental details

Crystal data
Chemical formulaC16H22O2
Mr246.34
Crystal system, space groupMonoclinic, P21/c
Temperature (K)113
a, b, c (Å)7.613 (2), 5.7513 (15), 31.085 (9)
β (°) 94.674 (4)
V3)1356.5 (6)
Z4
Radiation typeMo Kα
µ (mm1)0.08
Crystal size (mm)0.20 × 0.18 × 0.10
Data collection
DiffractometerRigaku Saturn CCD area-detector
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku/MSC, 2009)
Tmin, Tmax0.985, 0.992
No. of measured, independent and
observed [I > 2σ(I)] reflections
13145, 3235, 2576
Rint0.042
(sin θ/λ)max1)0.658
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.139, 1.06
No. of reflections3235
No. of parameters165
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.25, 0.18

Computer programs: CrystalClear-SM Expert (Rigaku/MSC, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

 

References

First citationRigaku/MSC (2009). CrystalClear-SM Expert and CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.
First citationShao, H., Gao, Y. L., Lou, Y. Y., Wang, Y. L., Liu, W., Xu, W. R., Wang, J. W., Zhao, G. L. & Tang, L. D. (2011). Chin. J. Org. Chem. 31, 836–842.  CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationWang, L., Chang, Z., Ding, C., Shao, H. & Sun, J. (2011). Acta Cryst. E67, o1173.  Web of Science CSD CrossRef IUCr Journals
First citationWashburn, W. N. (2009). J. Med. Chem. 52, 1785–1794.  Web of Science CrossRef PubMed CAS
First citationZhao, W. J., Shi, Y. H., Zhao, G. L., Wang, Y. L., Shao, H., Tang, L. D. & Wang, J. W. (2011). Chin. Chem. Lett. 22, 1215–1218.  CAS

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