(4-Ethyl­cyclo­hex­yl)(4-meth­oxy­phen­yl)methanone

Ding, C.-L.; Wu, Y.-J.; Zhang, Y.; Zhou, L.

doi:10.1107/S1600536813003279

organic compounds

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ISSN: 2056-9890

Volume 69| Part 3| March 2013| Page o348

doi:10.1107/S1600536813003279

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(4-Ethylcyclohexyl)(4-methoxyphenyl)methanone

Chun-Lei Ding,^a ^* Yong-Jie Wu,^b Yi Zhang ^a and Li Zhou ^a

^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 ); Zhao et al. (2011 ); Shao et al. (2011 ). For the crystal structures of cyclohexyl derivertives, see: Wang et al. (2011 ).

Experimental

Crystal data

C₁₆H₂₂O₂
M_r = 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) T_min = 0.985, T_max = 0.992
13145 measured reflections
3235 independent reflections
2576 reflections with I > 2σ(I)
R_int = 0.042

Refinement

R[F² > 2σ(F²)] = 0.050
wR(F²) = 0.139
S = 1.06
3235 reflections
165 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: CrystalClear-SM Expert (Rigaku/MSC, 2009); cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; 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/S1600536813003279/hg5288sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813003279/hg5288Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813003279/hg5288Isup3.cml

checkCIF report

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 0^oC 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).

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

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

C₁₆H₂₂O₂	F(000) = 536
M_r = 246.34	D_x = 1.206 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3595 reflections
a = 7.613 (2) Å	θ = 1.3–27.9°
b = 5.7513 (15) Å	µ = 0.08 mm⁻¹
c = 31.085 (9) Å	T = 113 K
β = 94.674 (4)°	Prism, colorless
V = 1356.5 (6) Å³	0.20 × 0.18 × 0.10 mm
Z = 4

Data collection top

Rigaku Saturn CCD area-detector diffractometer	3235 independent reflections
Radiation source: rotating anode	2576 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.042
Detector resolution: 14.63 pixels mm^-1	θ_max = 27.9°, θ_min = 1.3°
ω and ϕ scans	h = −9→10
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2009)	k = −6→7
T_min = 0.985, T_max = 0.992	l = −40→40
13145 measured reflections

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.139	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0684P)² + 0.0117P] where P = (F_o² + 2F_c²)/3
3235 reflections	(Δ/σ)_max = 0.001
165 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₆H₂₂O₂	V = 1356.5 (6) Å³
M_r = 246.34	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.613 (2) Å	µ = 0.08 mm⁻¹
b = 5.7513 (15) Å	T = 113 K
c = 31.085 (9) Å	0.20 × 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)
T_min = 0.985, T_max = 0.992	R_int = 0.042
13145 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	0 restraints
wR(F²) = 0.139	H-atom parameters constrained
S = 1.06	Δρ_max = 0.25 e Å⁻³
3235 reflections	Δρ_min = −0.18 e Å⁻³
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

	x	y	z	U_iso*/U_eq
O1	0.34006 (12)	0.74119 (17)	0.16856 (3)	0.0272 (3)
O2	0.05937 (15)	0.53751 (18)	0.34949 (3)	0.0352 (3)
C1	0.3969 (2)	0.9518 (3)	0.14967 (4)	0.0316 (4)
H1A	0.3107	1.0750	0.1536	0.047*
H1B	0.4073	0.9276	0.1188	0.047*
H1C	0.5117	0.9974	0.1637	0.047*
C2	0.29562 (17)	0.7517 (2)	0.21018 (4)	0.0215 (3)
C3	0.20950 (17)	0.5560 (2)	0.22446 (4)	0.0229 (3)
H3	0.1869	0.4273	0.2057	0.028*
C4	0.15706 (17)	0.5488 (2)	0.26592 (4)	0.0212 (3)
H4	0.0986	0.4147	0.2755	0.025*
C5	0.18896 (17)	0.7370 (2)	0.29413 (4)	0.0198 (3)
C6	0.27745 (17)	0.9302 (2)	0.27951 (4)	0.0215 (3)
H6	0.3013	1.0582	0.2984	0.026*
C7	0.33165 (18)	0.9393 (2)	0.23779 (4)	0.0215 (3)
H7	0.3923	1.0718	0.2283	0.026*
C8	0.12147 (18)	0.7220 (2)	0.33787 (4)	0.0229 (3)
C9	0.13144 (17)	0.9305 (2)	0.36774 (4)	0.0213 (3)
H9	0.1151	1.0748	0.3499	0.026*
C10	−0.01352 (18)	0.9211 (2)	0.39925 (4)	0.0245 (3)
H10A	−0.1303	0.9292	0.3828	0.029*
H10B	−0.0061	0.7714	0.4150	0.029*
C11	0.00388 (17)	1.1215 (2)	0.43170 (4)	0.0239 (3)
H11A	−0.0890	1.1069	0.4521	0.029*
H11B	−0.0144	1.2708	0.4161	0.029*
C12	0.18477 (18)	1.1241 (2)	0.45716 (4)	0.0219 (3)
H12	0.2001	0.9730	0.4730	0.026*
C13	0.32707 (18)	1.1398 (2)	0.42528 (4)	0.0235 (3)
H13A	0.4446	1.1378	0.4414	0.028*
H13B	0.3147	1.2892	0.4095	0.028*
C14	0.31498 (18)	0.9391 (2)	0.39280 (4)	0.0233 (3)
H14A	0.3376	0.7903	0.4083	0.028*
H14B	0.4064	0.9588	0.3722	0.028*
C15	0.19885 (19)	1.3203 (3)	0.49047 (4)	0.0264 (3)
H15A	0.2086	1.4700	0.4751	0.032*
H15B	0.0886	1.3248	0.5053	0.032*
C16	0.3545 (2)	1.2989 (3)	0.52446 (4)	0.0319 (4)
H16A	0.3385	1.1616	0.5424	0.048*
H16B	0.3609	1.4383	0.5427	0.048*
H16C	0.4639	1.2832	0.5101	0.048*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0309 (6)	0.0321 (6)	0.0196 (5)	−0.0005 (4)	0.0068 (4)	−0.0025 (4)
O2	0.0550 (7)	0.0257 (6)	0.0261 (6)	−0.0095 (5)	0.0099 (5)	0.0028 (4)
C1	0.0357 (9)	0.0380 (10)	0.0223 (7)	0.0010 (7)	0.0089 (6)	0.0029 (6)
C2	0.0185 (7)	0.0272 (8)	0.0186 (6)	0.0026 (6)	0.0004 (5)	−0.0004 (5)
C3	0.0230 (7)	0.0221 (8)	0.0234 (7)	0.0009 (6)	0.0000 (5)	−0.0032 (5)
C4	0.0197 (7)	0.0188 (7)	0.0247 (7)	−0.0007 (5)	−0.0008 (5)	0.0022 (5)
C5	0.0200 (7)	0.0209 (7)	0.0180 (6)	0.0014 (5)	−0.0012 (5)	0.0012 (5)
C6	0.0231 (7)	0.0220 (8)	0.0188 (7)	0.0000 (6)	−0.0010 (5)	−0.0005 (5)
C7	0.0212 (7)	0.0216 (8)	0.0218 (7)	−0.0007 (5)	0.0018 (5)	0.0016 (5)
C8	0.0233 (7)	0.0232 (8)	0.0216 (7)	0.0001 (6)	−0.0008 (5)	0.0038 (5)
C9	0.0252 (8)	0.0221 (8)	0.0167 (6)	−0.0005 (6)	0.0022 (5)	0.0025 (5)
C10	0.0237 (8)	0.0296 (8)	0.0203 (7)	−0.0025 (6)	0.0021 (5)	0.0020 (5)
C11	0.0224 (7)	0.0300 (8)	0.0198 (6)	0.0019 (6)	0.0057 (5)	0.0019 (5)
C12	0.0251 (7)	0.0233 (8)	0.0177 (6)	0.0006 (6)	0.0034 (5)	0.0015 (5)
C13	0.0229 (7)	0.0257 (8)	0.0221 (7)	−0.0018 (6)	0.0026 (5)	0.0001 (5)
C14	0.0230 (7)	0.0267 (8)	0.0207 (7)	0.0005 (6)	0.0043 (5)	−0.0007 (5)
C15	0.0316 (8)	0.0260 (8)	0.0221 (7)	0.0012 (6)	0.0043 (6)	−0.0015 (5)
C16	0.0367 (9)	0.0360 (9)	0.0230 (7)	−0.0035 (7)	0.0025 (6)	−0.0045 (6)

Geometric parameters (Å, º) top

O1—C2	1.3649 (15)	C10—C11	1.5302 (18)
O1—C1	1.4286 (16)	C10—H10A	0.9900
O2—C8	1.2281 (16)	C10—H10B	0.9900
C1—H1A	0.9800	C11—C12	1.5313 (18)
C1—H1B	0.9800	C11—H11A	0.9900
C1—H1C	0.9800	C11—H11B	0.9900
C2—C7	1.3923 (18)	C12—C13	1.5294 (18)
C2—C3	1.3933 (19)	C12—C15	1.5295 (18)
C3—C4	1.3805 (18)	C12—H12	1.0000
C3—H3	0.9500	C13—C14	1.5315 (18)
C4—C5	1.4017 (18)	C13—H13A	0.9900
C4—H4	0.9500	C13—H13B	0.9900
C5—C6	1.3941 (18)	C14—H14A	0.9900
C5—C8	1.4946 (18)	C14—H14B	0.9900
C6—C7	1.3935 (17)	C15—C16	1.5269 (19)
C6—H6	0.9500	C15—H15A	0.9900
C7—H7	0.9500	C15—H15B	0.9900
C8—C9	1.5146 (18)	C16—H16A	0.9800
C9—C10	1.5352 (18)	C16—H16B	0.9800
C9—C14	1.5441 (18)	C16—H16C	0.9800
C9—H9	1.0000

C2—O1—C1	117.31 (11)	C9—C10—H10B	109.3
O1—C1—H1A	109.5	H10A—C10—H10B	108.0
O1—C1—H1B	109.5	C10—C11—C12	111.94 (11)
H1A—C1—H1B	109.5	C10—C11—H11A	109.2
O1—C1—H1C	109.5	C12—C11—H11A	109.2
H1A—C1—H1C	109.5	C10—C11—H11B	109.2
H1B—C1—H1C	109.5	C12—C11—H11B	109.2
O1—C2—C7	124.55 (12)	H11A—C11—H11B	107.9
O1—C2—C3	115.20 (12)	C13—C12—C15	112.37 (11)
C7—C2—C3	120.25 (12)	C13—C12—C11	108.69 (11)
C4—C3—C2	120.06 (12)	C15—C12—C11	111.55 (11)
C4—C3—H3	120.0	C13—C12—H12	108.0
C2—C3—H3	120.0	C15—C12—H12	108.0
C3—C4—C5	120.83 (13)	C11—C12—H12	108.0
C3—C4—H4	119.6	C12—C13—C14	112.00 (11)
C5—C4—H4	119.6	C12—C13—H13A	109.2
C6—C5—C4	118.36 (12)	C14—C13—H13A	109.2
C6—C5—C8	123.61 (12)	C12—C13—H13B	109.2
C4—C5—C8	118.01 (12)	C14—C13—H13B	109.2
C7—C6—C5	121.40 (12)	H13A—C13—H13B	107.9
C7—C6—H6	119.3	C13—C14—C9	111.10 (11)
C5—C6—H6	119.3	C13—C14—H14A	109.4
C2—C7—C6	119.08 (12)	C9—C14—H14A	109.4
C2—C7—H7	120.5	C13—C14—H14B	109.4
C6—C7—H7	120.5	C9—C14—H14B	109.4
O2—C8—C5	119.12 (12)	H14A—C14—H14B	108.0
O2—C8—C9	120.34 (12)	C16—C15—C12	114.64 (12)
C5—C8—C9	120.54 (12)	C16—C15—H15A	108.6
C8—C9—C10	111.14 (11)	C12—C15—H15A	108.6
C8—C9—C14	109.43 (11)	C16—C15—H15B	108.6
C10—C9—C14	110.31 (11)	C12—C15—H15B	108.6
C8—C9—H9	108.6	H15A—C15—H15B	107.6
C10—C9—H9	108.6	C15—C16—H16A	109.5
C14—C9—H9	108.6	C15—C16—H16B	109.5
C11—C10—C9	111.47 (11)	H16A—C16—H16B	109.5
C11—C10—H10A	109.3	C15—C16—H16C	109.5
C9—C10—H10A	109.3	H16A—C16—H16C	109.5
C11—C10—H10B	109.3	H16B—C16—H16C	109.5

C1—O1—C2—C7	−12.28 (19)	O2—C8—C9—C10	−27.46 (17)
C1—O1—C2—C3	168.14 (11)	C5—C8—C9—C10	153.29 (12)
O1—C2—C3—C4	−179.40 (11)	O2—C8—C9—C14	94.61 (15)
C7—C2—C3—C4	1.0 (2)	C5—C8—C9—C14	−84.64 (14)
C2—C3—C4—C5	0.1 (2)	C8—C9—C10—C11	175.81 (10)
C3—C4—C5—C6	−1.00 (19)	C14—C9—C10—C11	54.25 (14)
C3—C4—C5—C8	177.29 (12)	C9—C10—C11—C12	−56.99 (14)
C4—C5—C6—C7	0.78 (19)	C10—C11—C12—C13	57.33 (14)
C8—C5—C6—C7	−177.40 (12)	C10—C11—C12—C15	−178.23 (11)
O1—C2—C7—C6	179.23 (12)	C15—C12—C13—C14	178.48 (10)
C3—C2—C7—C6	−1.21 (19)	C11—C12—C13—C14	−57.57 (14)
C5—C6—C7—C2	0.3 (2)	C12—C13—C14—C9	57.13 (15)
C6—C5—C8—O2	−173.42 (12)	C8—C9—C14—C13	−176.81 (11)
C4—C5—C8—O2	8.38 (19)	C10—C9—C14—C13	−54.24 (14)
C6—C5—C8—C9	5.83 (19)	C13—C12—C15—C16	−72.27 (15)
C4—C5—C8—C9	−172.36 (12)	C11—C12—C15—C16	165.39 (12)

Experimental details

Crystal data
Chemical formula	C₁₆H₂₂O₂
M_r	246.34
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	113
a, b, c (Å)	7.613 (2), 5.7513 (15), 31.085 (9)
β (°)	94.674 (4)
V (Å³)	1356.5 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.20 × 0.18 × 0.10

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2009)
T_min, T_max	0.985, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	13145, 3235, 2576
R_int	0.042
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.139, 1.06
No. of reflections	3235
No. of parameters	165
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.18

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

References

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