(5-Bromo-2-meth­oxy­phen­yl)(4-ethyl­cyclo­hex­yl)methanone

Wang, L.; Chang, Z.; Ding, C.; Shao, H.; Sun, J.

doi:10.1107/S1600536811013687

organic compounds

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ISSN: 2056-9890

Volume 67| Part 5| May 2011| Page o1173

doi:10.1107/S1600536811013687

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(5-Bromo-2-methoxyphenyl)(4-ethylcyclohexyl)methanone

Ling Wang,^a Ziqian Chang,^a Chunlei Ding,^a Hua Shao ^b and Jianzi Sun ^a ^*

^aPharmacy Department of the Second Artillery General Hospital, Beijing 100088, People's Republic of China, and ^bTianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, People's Republic of China
^*Correspondence e-mail: jzs2011@yahoo.cn

(Received 26 March 2011; accepted 12 April 2011; online 16 April 2011)

In the title compound, C₁₆H₂₁BrO₂, the cyclohexane ring is in a chair conformation and its least-squares plane is at an angle of 61.3 (9)° to the benzene ring. The crystal packing is stabilized by weak π–π stacking interactions [centroid–centroid distance = 3.697 (9) Å] between the bromomethoxyphenyl rings of neighbouring molecules.

Related literature

For the antihyperglycemic activity of SGLT2 inhibitors, see: Gao et al. (2010 ); Meng et al. (2008 ); Shao et al. (2010 ). For bond-length data, see: Allen et al. (1987 ).

Experimental

Crystal data

C₁₆H₂₁BrO₂
M_r = 325.24
Monoclinic, P 2₁ /c
a = 14.204 (3) Å
b = 11.276 (2) Å
c = 9.604 (2) Å
β = 102.329 (4)°
V = 1502.8 (6) Å³
Z = 4
Mo Kα radiation
μ = 2.73 mm⁻¹
T = 113 K
0.26 × 0.22 × 0.20 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2007 ) T_min = 0.537, T_max = 0.611
13836 measured reflections
3588 independent reflections
2581 reflections with I > 2σ(I)
R_int = 0.033

Refinement

R[F² > 2σ(F²)] = 0.024
wR(F²) = 0.058
S = 1.04
3588 reflections
174 parameters
H-atom parameters constrained
Δρ_max = 0.52 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Data collection: CrystalClear (Rigaku, 2007); cell refinement: CrystalClear; data reduction: CrystalClear; 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/S1600536811013687/bx2347sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811013687/bx2347Isup2.hkl

checkCIF report

Comment top

SGLT2 inhibitors are a class of promising anti-hyperglycemic agents, and a variety of SGLT2 inhibitors are now in clinical trials (Meng et al., 2008). The title compound was a crucial intermediate, the aglycon of the C-glucoside SGLT2 inhibitors, for the synthesis of novel C-glucoside SGLT2 inhibitors during the development of our own SGLT2 inhibitors (Gao et al., 2010; Shao et al., 2010). The title compound, C₁₆H₂₁BrO₂, bond lengths are normal (Allen et al., 1987). The C═O bond of the title compound, C₁₆H₂₁BrO₂, is non-coplanar with the benzene ring. The cyclohexane ring is in the chair conformation and its least-squares plane is at an angle of 61.3 (9)° to the benzene ring. No classic hydrogen bonds were found, the crystal packing is stabilized by one weak π–π stacking interaction [centroid-to-centroid distance = 3.697 (9) Å, Cg1 is centroid of benzene ring (C2—C7), Symmetry code:1 - x, -y, 1 - z].

Related literature top

For the antihyperglycemic activity of SGLT2 inhibitors, see: Gao et al. (2010); Meng et al. (2008); Shao et al. (2010). For bond-length data, see: Allen et al. (1987).

Experimental top

A dried 100-ml round-bottomed flask was charged with 1.75 g (10 mmol) of trans-4-ethylcyclohexanecarboxylic acid chloride, 1.87 g (10 mmol) of 4-bromoanisole and 20 ml of dried dichloromethane, and the mixture was stirred on an ice-water bath, followed by addition of 1.33 g (10 mmol) of anhydrous aluminium chloride in a portion wise manner. After addition, the reaction mixture was stirred at room temperature overnight and poured into 300 ml of ice-water. The mixture thus formed was extracted with three 50-ml portions of dichloromethane, and the combined exacts were washed successively with 1% hydrochloric acid and saturated brine, dried over sodium sulfate and evaporated on a rotary evaporator to afford the crude title compound. Pure title compound was obtained by column chromatography. Crystals suitable for X-ray diffraction were obtained through slow evaporation of a solution of the pure title compound in dichloromethane/petroleum ether mixture (1/30 by volume).

Computing details top

Data collection: CrystalClear (Rigaku, 2007); cell refinement: CrystalClear (Rigaku, 2007); data reduction: CrystalClear (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXL97 (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of (I), with atom labels and 40% probability displacement ellipsoids for non-H atoms.

(5-Bromo-2-methoxyphenyl)(4-ethylcyclohexyl)methanone top

Crystal data top

C₁₆H₂₁BrO₂	F(000) = 672
M_r = 325.24	D_x = 1.438 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5413 reflections
a = 14.204 (3) Å	θ = 2.2–27.9°
b = 11.276 (2) Å	µ = 2.73 mm⁻¹
c = 9.604 (2) Å	T = 113 K
β = 102.329 (4)°	Prism, colorless
V = 1502.8 (6) Å³	0.26 × 0.22 × 0.20 mm
Z = 4

Data collection top

Rigaku Saturn CCD area-detector diffractometer	3588 independent reflections
Radiation source: rotating anode	2581 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.033
Detector resolution: 14.63 pixels mm^-1	θ_max = 27.9°, θ_min = 2.3°
ω and ϕ scans	h = −18→18
Absorption correction: multi-scan (CrystalClear; Rigaku, 2007)	k = −14→11
T_min = 0.537, T_max = 0.611	l = −12→12
13836 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)] = 0.024	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.058	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.026P)²] where P = (F_o² + 2F_c²)/3
3588 reflections	(Δ/σ)_max = 0.001
174 parameters	Δρ_max = 0.52 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³

Crystal data top

C₁₆H₂₁BrO₂	V = 1502.8 (6) Å³
M_r = 325.24	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 14.204 (3) Å	µ = 2.73 mm⁻¹
b = 11.276 (2) Å	T = 113 K
c = 9.604 (2) Å	0.26 × 0.22 × 0.20 mm
β = 102.329 (4)°

Data collection top

Rigaku Saturn CCD area-detector diffractometer	3588 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2007)	2581 reflections with I > 2σ(I)
T_min = 0.537, T_max = 0.611	R_int = 0.033
13836 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.024	0 restraints
wR(F²) = 0.058	H-atom parameters constrained
S = 1.04	Δρ_max = 0.52 e Å⁻³
3588 reflections	Δρ_min = −0.28 e Å⁻³
174 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
Br1	0.359389 (12)	1.039199 (15)	0.078211 (19)	0.02887 (7)
O1	0.67370 (8)	1.14977 (9)	0.58965 (11)	0.0236 (3)
O2	0.71492 (8)	0.90082 (11)	0.30034 (13)	0.0339 (3)
C1	0.66083 (12)	1.24071 (14)	0.68801 (17)	0.0272 (4)
H1A	0.6506	1.3170	0.6382	0.041*
H1B	0.7184	1.2455	0.7650	0.041*
H1C	0.6047	1.2219	0.7281	0.041*
C2	0.59954 (11)	1.12527 (13)	0.47931 (16)	0.0176 (3)
C3	0.51379 (11)	1.19027 (13)	0.45009 (17)	0.0202 (4)
H3	0.5046	1.2526	0.5124	0.024*
C4	0.44236 (11)	1.16512 (13)	0.33205 (17)	0.0212 (4)
H4	0.3845	1.2102	0.3123	0.025*
C5	0.45613 (11)	1.07334 (14)	0.24293 (17)	0.0193 (4)
C6	0.54008 (11)	1.00793 (14)	0.26967 (17)	0.0181 (3)
H6	0.5482	0.9459	0.2063	0.022*
C7	0.61305 (11)	1.03146 (12)	0.38797 (16)	0.0160 (3)
C8	0.70157 (11)	0.95429 (13)	0.40477 (17)	0.0192 (3)
C9	0.77081 (11)	0.93956 (12)	0.54697 (17)	0.0170 (3)
H9	0.7377	0.9641	0.6244	0.020*
C10	0.80398 (11)	0.81086 (13)	0.57217 (17)	0.0205 (4)
H10A	0.7474	0.7589	0.5690	0.025*
H10B	0.8367	0.7853	0.4960	0.025*
C11	0.87275 (11)	0.79932 (13)	0.71633 (17)	0.0208 (4)
H11A	0.8930	0.7155	0.7317	0.025*
H11B	0.8386	0.8217	0.7921	0.025*
C12	0.96177 (11)	0.87687 (13)	0.72848 (17)	0.0205 (4)
H12	0.9971	0.8502	0.6545	0.025*
C13	0.93087 (11)	1.00610 (14)	0.69645 (18)	0.0232 (4)
H13A	0.9005	1.0362	0.7731	0.028*
H13B	0.9887	1.0550	0.6959	0.028*
C14	0.86004 (10)	1.01921 (14)	0.55324 (17)	0.0205 (4)
H14A	0.8924	0.9971	0.4753	0.025*
H14B	0.8394	1.1030	0.5393	0.025*
C15	1.02894 (11)	0.86209 (15)	0.87409 (18)	0.0268 (4)
H15A	0.9958	0.8927	0.9476	0.032*
H15B	1.0405	0.7763	0.8923	0.032*
C16	1.12570 (12)	0.92389 (19)	0.8919 (2)	0.0430 (5)
H16A	1.1575	0.8988	0.8157	0.064*
H16B	1.1662	0.9029	0.9846	0.064*
H16C	1.1159	1.0099	0.8870	0.064*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.02108 (10)	0.03198 (11)	0.02822 (11)	0.00216 (7)	−0.00667 (7)	0.00102 (8)
O1	0.0236 (6)	0.0242 (6)	0.0208 (6)	0.0053 (5)	−0.0002 (5)	−0.0083 (5)
O2	0.0284 (7)	0.0513 (8)	0.0192 (7)	0.0171 (6)	−0.0011 (6)	−0.0109 (6)
C1	0.0309 (10)	0.0257 (9)	0.0242 (9)	0.0016 (8)	0.0045 (8)	−0.0107 (8)
C2	0.0187 (8)	0.0196 (8)	0.0147 (8)	−0.0011 (6)	0.0039 (7)	0.0027 (7)
C3	0.0238 (9)	0.0182 (8)	0.0206 (9)	0.0022 (7)	0.0094 (7)	0.0016 (7)
C4	0.0177 (8)	0.0209 (9)	0.0265 (9)	0.0031 (6)	0.0081 (7)	0.0066 (7)
C5	0.0168 (8)	0.0215 (8)	0.0178 (8)	−0.0019 (6)	−0.0002 (7)	0.0053 (7)
C6	0.0209 (9)	0.0173 (8)	0.0162 (8)	−0.0005 (6)	0.0040 (7)	0.0027 (6)
C7	0.0159 (7)	0.0164 (8)	0.0162 (8)	−0.0005 (6)	0.0044 (6)	0.0034 (7)
C8	0.0164 (8)	0.0219 (8)	0.0188 (8)	0.0005 (6)	0.0028 (7)	−0.0019 (7)
C9	0.0151 (8)	0.0199 (8)	0.0157 (8)	−0.0003 (6)	0.0027 (6)	−0.0017 (7)
C10	0.0175 (8)	0.0192 (8)	0.0240 (9)	−0.0001 (6)	0.0029 (7)	−0.0020 (7)
C11	0.0215 (8)	0.0162 (8)	0.0235 (9)	0.0013 (6)	0.0024 (7)	0.0014 (7)
C12	0.0169 (8)	0.0229 (9)	0.0202 (9)	0.0017 (6)	0.0007 (7)	−0.0016 (7)
C13	0.0180 (9)	0.0205 (8)	0.0283 (10)	−0.0041 (7)	−0.0011 (8)	0.0038 (7)
C14	0.0178 (8)	0.0208 (9)	0.0225 (9)	−0.0016 (6)	0.0036 (7)	0.0036 (7)
C15	0.0244 (9)	0.0262 (9)	0.0259 (10)	0.0017 (7)	−0.0035 (8)	0.0000 (8)
C16	0.0230 (10)	0.0583 (13)	0.0406 (13)	−0.0021 (9)	−0.0089 (9)	0.0032 (10)

Geometric parameters (Å, º) top

Br1—C5	1.9002 (16)	C10—C11	1.520 (2)
O1—C2	1.3536 (17)	C10—H10A	0.9900
O1—C1	1.4322 (17)	C10—H10B	0.9900
O2—C8	1.2192 (18)	C11—C12	1.521 (2)
C1—H1A	0.9800	C11—H11A	0.9900
C1—H1B	0.9800	C11—H11B	0.9900
C1—H1C	0.9800	C12—C15	1.524 (2)
C2—C3	1.398 (2)	C12—C13	1.534 (2)
C2—C7	1.413 (2)	C12—H12	1.0000
C3—C4	1.380 (2)	C13—C14	1.528 (2)
C3—H3	0.9500	C13—H13A	0.9900
C4—C5	1.383 (2)	C13—H13B	0.9900
C4—H4	0.9500	C14—H14A	0.9900
C5—C6	1.379 (2)	C14—H14B	0.9900
C6—C7	1.390 (2)	C15—C16	1.518 (2)
C6—H6	0.9500	C15—H15A	0.9900
C7—C8	1.509 (2)	C15—H15B	0.9900
C8—C9	1.512 (2)	C16—H16A	0.9800
C9—C10	1.529 (2)	C16—H16B	0.9800
C9—C14	1.544 (2)	C16—H16C	0.9800
C9—H9	1.0000

C2—O1—C1	118.36 (12)	C9—C10—H10B	109.7
O1—C1—H1A	109.5	H10A—C10—H10B	108.2
O1—C1—H1B	109.5	C10—C11—C12	112.50 (13)
H1A—C1—H1B	109.5	C10—C11—H11A	109.1
O1—C1—H1C	109.5	C12—C11—H11A	109.1
H1A—C1—H1C	109.5	C10—C11—H11B	109.1
H1B—C1—H1C	109.5	C12—C11—H11B	109.1
O1—C2—C3	123.32 (14)	H11A—C11—H11B	107.8
O1—C2—C7	116.91 (14)	C11—C12—C15	110.78 (13)
C3—C2—C7	119.73 (15)	C11—C12—C13	109.46 (12)
C4—C3—C2	120.91 (15)	C15—C12—C13	112.58 (13)
C4—C3—H3	119.5	C11—C12—H12	108.0
C2—C3—H3	119.5	C15—C12—H12	108.0
C3—C4—C5	119.06 (15)	C13—C12—H12	108.0
C3—C4—H4	120.5	C14—C13—C12	112.18 (13)
C5—C4—H4	120.5	C14—C13—H13A	109.2
C6—C5—C4	121.06 (15)	C12—C13—H13A	109.2
C6—C5—Br1	119.32 (12)	C14—C13—H13B	109.2
C4—C5—Br1	119.61 (12)	C12—C13—H13B	109.2
C5—C6—C7	120.96 (15)	H13A—C13—H13B	107.9
C5—C6—H6	119.5	C13—C14—C9	110.86 (13)
C7—C6—H6	119.5	C13—C14—H14A	109.5
C6—C7—C2	118.28 (14)	C9—C14—H14A	109.5
C6—C7—C8	115.86 (14)	C13—C14—H14B	109.5
C2—C7—C8	125.85 (14)	C9—C14—H14B	109.5
O2—C8—C7	118.01 (14)	H14A—C14—H14B	108.1
O2—C8—C9	120.22 (14)	C16—C15—C12	115.32 (15)
C7—C8—C9	121.75 (14)	C16—C15—H15A	108.4
C8—C9—C10	111.48 (13)	C12—C15—H15A	108.4
C8—C9—C14	109.97 (13)	C16—C15—H15B	108.4
C10—C9—C14	108.86 (13)	C12—C15—H15B	108.4
C8—C9—H9	108.8	H15A—C15—H15B	107.5
C10—C9—H9	108.8	C15—C16—H16A	109.5
C14—C9—H9	108.8	C15—C16—H16B	109.5
C11—C10—C9	109.99 (12)	H16A—C16—H16B	109.5
C11—C10—H10A	109.7	C15—C16—H16C	109.5
C9—C10—H10A	109.7	H16A—C16—H16C	109.5
C11—C10—H10B	109.7	H16B—C16—H16C	109.5

C1—O1—C2—C3	5.2 (2)	C2—C7—C8—C9	22.2 (2)
C1—O1—C2—C7	−177.20 (13)	O2—C8—C9—C10	−39.5 (2)
O1—C2—C3—C4	176.77 (14)	C7—C8—C9—C10	138.54 (14)
C7—C2—C3—C4	−0.8 (2)	O2—C8—C9—C14	81.31 (18)
C2—C3—C4—C5	0.7 (2)	C7—C8—C9—C14	−100.62 (16)
C3—C4—C5—C6	−0.6 (2)	C8—C9—C10—C11	−179.57 (13)
C3—C4—C5—Br1	−178.97 (11)	C14—C9—C10—C11	58.95 (17)
C4—C5—C6—C7	0.7 (2)	C9—C10—C11—C12	−59.46 (17)
Br1—C5—C6—C7	179.06 (11)	C10—C11—C12—C15	−179.67 (13)
C5—C6—C7—C2	−0.8 (2)	C10—C11—C12—C13	55.60 (18)
C5—C6—C7—C8	−179.56 (14)	C11—C12—C13—C14	−53.76 (18)
O1—C2—C7—C6	−176.87 (13)	C15—C12—C13—C14	−177.44 (14)
C3—C2—C7—C6	0.9 (2)	C12—C13—C14—C9	56.16 (18)
O1—C2—C7—C8	1.7 (2)	C8—C9—C14—C13	179.77 (13)
C3—C2—C7—C8	179.47 (14)	C10—C9—C14—C13	−57.84 (17)
C6—C7—C8—O2	18.9 (2)	C11—C12—C15—C16	172.94 (15)
C2—C7—C8—O2	−159.73 (16)	C13—C12—C15—C16	−64.1 (2)
C6—C7—C8—C9	−159.20 (14)

Experimental details

Crystal data
Chemical formula	C₁₆H₂₁BrO₂
M_r	325.24
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	113
a, b, c (Å)	14.204 (3), 11.276 (2), 9.604 (2)
β (°)	102.329 (4)
V (Å³)	1502.8 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	2.73
Crystal size (mm)	0.26 × 0.22 × 0.20

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2007)
T_min, T_max	0.537, 0.611
No. of measured, independent and observed [I > 2σ(I)] reflections	13836, 3588, 2581
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.024, 0.058, 1.04
No. of reflections	3588
No. of parameters	174
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.52, −0.28

Computer programs: CrystalClear (Rigaku, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

References

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