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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 5| May 2011| Page o1173

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

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 ππ 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[Gao, Y. L., Zhao, G. L., Liu, W., Wang, Y. L., Xu, W. R. & Wang, J. W. (2010). Chin. J. Chem. 28, 605-612.]); Meng et al. (2008[Meng, M., et al. (2008). J. Med. Chem. 51, 1145-1149.]); Shao et al. (2010[Shao, H., Zhao, G. L., Liu, W., Wang, Y. L., Xu, W. R. & Tang, L. D. (2010). Chin. J. Synth. Chem. 18, 389-392.]). For bond-length data, see: Allen et al. (1987[Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.]).

[Scheme 1]

Experimental

Crystal data
  • C16H21BrO2

  • Mr = 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[Rigaku (2007). CrystalClear. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.537, Tmax = 0.611

  • 13836 measured reflections

  • 3588 independent reflections

  • 2581 reflections with I > 2σ(I)

  • Rint = 0.033

Refinement
  • R[F2 > 2σ(F2)] = 0.024

  • wR(F2) = 0.058

  • S = 1.04

  • 3588 reflections

  • 174 parameters

  • H-atom parameters constrained

  • Δρmax = 0.52 e Å−3

  • Δρmin = −0.28 e Å−3

Data collection: CrystalClear (Rigaku, 2007[Rigaku (2007). CrystalClear. Rigaku Corporation, Tokyo, Japan.]); cell refinement: CrystalClear; data reduction: CrystalClear; 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 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 CO 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 ππ 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).

Refinement top

H atoms were positioned geometrically and refined using a riding model, with C—H = 0.95 to 1.00 Å; with Uiso(H) = 1.2 times Ueq(C) and 1.5 times Ueq(C)for methyl H atoms.

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
[Figure 1] 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
C16H21BrO2F(000) = 672
Mr = 325.24Dx = 1.438 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 5413 reflections
a = 14.204 (3) Åθ = 2.2–27.9°
b = 11.276 (2) ŵ = 2.73 mm1
c = 9.604 (2) ÅT = 113 K
β = 102.329 (4)°Prism, colorless
V = 1502.8 (6) Å30.26 × 0.22 × 0.20 mm
Z = 4
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
3588 independent reflections
Radiation source: rotating anode2581 reflections with I > 2σ(I)
Multilayer monochromatorRint = 0.033
Detector resolution: 14.63 pixels mm-1θmax = 27.9°, θmin = 2.3°
ω and ϕ scansh = 1818
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2007)
k = 1411
Tmin = 0.537, Tmax = 0.611l = 1212
13836 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)] = 0.024Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.058H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.026P)2]
where P = (Fo2 + 2Fc2)/3
3588 reflections(Δ/σ)max = 0.001
174 parametersΔρmax = 0.52 e Å3
0 restraintsΔρmin = 0.28 e Å3
Crystal data top
C16H21BrO2V = 1502.8 (6) Å3
Mr = 325.24Z = 4
Monoclinic, P21/cMo Kα radiation
a = 14.204 (3) ŵ = 2.73 mm1
b = 11.276 (2) ÅT = 113 K
c = 9.604 (2) Å0.26 × 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)
Tmin = 0.537, Tmax = 0.611Rint = 0.033
13836 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0240 restraints
wR(F2) = 0.058H-atom parameters constrained
S = 1.04Δρmax = 0.52 e Å3
3588 reflectionsΔρmin = 0.28 e Å3
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
xyzUiso*/Ueq
Br10.359389 (12)1.039199 (15)0.078211 (19)0.02887 (7)
O10.67370 (8)1.14977 (9)0.58965 (11)0.0236 (3)
O20.71492 (8)0.90082 (11)0.30034 (13)0.0339 (3)
C10.66083 (12)1.24071 (14)0.68801 (17)0.0272 (4)
H1A0.65061.31700.63820.041*
H1B0.71841.24550.76500.041*
H1C0.60471.22190.72810.041*
C20.59954 (11)1.12527 (13)0.47931 (16)0.0176 (3)
C30.51379 (11)1.19027 (13)0.45009 (17)0.0202 (4)
H30.50461.25260.51240.024*
C40.44236 (11)1.16512 (13)0.33205 (17)0.0212 (4)
H40.38451.21020.31230.025*
C50.45613 (11)1.07334 (14)0.24293 (17)0.0193 (4)
C60.54008 (11)1.00793 (14)0.26967 (17)0.0181 (3)
H60.54820.94590.20630.022*
C70.61305 (11)1.03146 (12)0.38797 (16)0.0160 (3)
C80.70157 (11)0.95429 (13)0.40477 (17)0.0192 (3)
C90.77081 (11)0.93956 (12)0.54697 (17)0.0170 (3)
H90.73770.96410.62440.020*
C100.80398 (11)0.81086 (13)0.57217 (17)0.0205 (4)
H10A0.74740.75890.56900.025*
H10B0.83670.78530.49600.025*
C110.87275 (11)0.79932 (13)0.71633 (17)0.0208 (4)
H11A0.89300.71550.73170.025*
H11B0.83860.82170.79210.025*
C120.96177 (11)0.87687 (13)0.72848 (17)0.0205 (4)
H120.99710.85020.65450.025*
C130.93087 (11)1.00610 (14)0.69645 (18)0.0232 (4)
H13A0.90051.03620.77310.028*
H13B0.98871.05500.69590.028*
C140.86004 (10)1.01921 (14)0.55324 (17)0.0205 (4)
H14A0.89240.99710.47530.025*
H14B0.83941.10300.53930.025*
C151.02894 (11)0.86209 (15)0.87409 (18)0.0268 (4)
H15A0.99580.89270.94760.032*
H15B1.04050.77630.89230.032*
C161.12570 (12)0.92389 (19)0.8919 (2)0.0430 (5)
H16A1.15750.89880.81570.064*
H16B1.16620.90290.98460.064*
H16C1.11591.00990.88700.064*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.02108 (10)0.03198 (11)0.02822 (11)0.00216 (7)0.00667 (7)0.00102 (8)
O10.0236 (6)0.0242 (6)0.0208 (6)0.0053 (5)0.0002 (5)0.0083 (5)
O20.0284 (7)0.0513 (8)0.0192 (7)0.0171 (6)0.0011 (6)0.0109 (6)
C10.0309 (10)0.0257 (9)0.0242 (9)0.0016 (8)0.0045 (8)0.0107 (8)
C20.0187 (8)0.0196 (8)0.0147 (8)0.0011 (6)0.0039 (7)0.0027 (7)
C30.0238 (9)0.0182 (8)0.0206 (9)0.0022 (7)0.0094 (7)0.0016 (7)
C40.0177 (8)0.0209 (9)0.0265 (9)0.0031 (6)0.0081 (7)0.0066 (7)
C50.0168 (8)0.0215 (8)0.0178 (8)0.0019 (6)0.0002 (7)0.0053 (7)
C60.0209 (9)0.0173 (8)0.0162 (8)0.0005 (6)0.0040 (7)0.0027 (6)
C70.0159 (7)0.0164 (8)0.0162 (8)0.0005 (6)0.0044 (6)0.0034 (7)
C80.0164 (8)0.0219 (8)0.0188 (8)0.0005 (6)0.0028 (7)0.0019 (7)
C90.0151 (8)0.0199 (8)0.0157 (8)0.0003 (6)0.0027 (6)0.0017 (7)
C100.0175 (8)0.0192 (8)0.0240 (9)0.0001 (6)0.0029 (7)0.0020 (7)
C110.0215 (8)0.0162 (8)0.0235 (9)0.0013 (6)0.0024 (7)0.0014 (7)
C120.0169 (8)0.0229 (9)0.0202 (9)0.0017 (6)0.0007 (7)0.0016 (7)
C130.0180 (9)0.0205 (8)0.0283 (10)0.0041 (7)0.0011 (8)0.0038 (7)
C140.0178 (8)0.0208 (9)0.0225 (9)0.0016 (6)0.0036 (7)0.0036 (7)
C150.0244 (9)0.0262 (9)0.0259 (10)0.0017 (7)0.0035 (8)0.0000 (8)
C160.0230 (10)0.0583 (13)0.0406 (13)0.0021 (9)0.0089 (9)0.0032 (10)
Geometric parameters (Å, º) top
Br1—C51.9002 (16)C10—C111.520 (2)
O1—C21.3536 (17)C10—H10A0.9900
O1—C11.4322 (17)C10—H10B0.9900
O2—C81.2192 (18)C11—C121.521 (2)
C1—H1A0.9800C11—H11A0.9900
C1—H1B0.9800C11—H11B0.9900
C1—H1C0.9800C12—C151.524 (2)
C2—C31.398 (2)C12—C131.534 (2)
C2—C71.413 (2)C12—H121.0000
C3—C41.380 (2)C13—C141.528 (2)
C3—H30.9500C13—H13A0.9900
C4—C51.383 (2)C13—H13B0.9900
C4—H40.9500C14—H14A0.9900
C5—C61.379 (2)C14—H14B0.9900
C6—C71.390 (2)C15—C161.518 (2)
C6—H60.9500C15—H15A0.9900
C7—C81.509 (2)C15—H15B0.9900
C8—C91.512 (2)C16—H16A0.9800
C9—C101.529 (2)C16—H16B0.9800
C9—C141.544 (2)C16—H16C0.9800
C9—H91.0000
C2—O1—C1118.36 (12)C9—C10—H10B109.7
O1—C1—H1A109.5H10A—C10—H10B108.2
O1—C1—H1B109.5C10—C11—C12112.50 (13)
H1A—C1—H1B109.5C10—C11—H11A109.1
O1—C1—H1C109.5C12—C11—H11A109.1
H1A—C1—H1C109.5C10—C11—H11B109.1
H1B—C1—H1C109.5C12—C11—H11B109.1
O1—C2—C3123.32 (14)H11A—C11—H11B107.8
O1—C2—C7116.91 (14)C11—C12—C15110.78 (13)
C3—C2—C7119.73 (15)C11—C12—C13109.46 (12)
C4—C3—C2120.91 (15)C15—C12—C13112.58 (13)
C4—C3—H3119.5C11—C12—H12108.0
C2—C3—H3119.5C15—C12—H12108.0
C3—C4—C5119.06 (15)C13—C12—H12108.0
C3—C4—H4120.5C14—C13—C12112.18 (13)
C5—C4—H4120.5C14—C13—H13A109.2
C6—C5—C4121.06 (15)C12—C13—H13A109.2
C6—C5—Br1119.32 (12)C14—C13—H13B109.2
C4—C5—Br1119.61 (12)C12—C13—H13B109.2
C5—C6—C7120.96 (15)H13A—C13—H13B107.9
C5—C6—H6119.5C13—C14—C9110.86 (13)
C7—C6—H6119.5C13—C14—H14A109.5
C6—C7—C2118.28 (14)C9—C14—H14A109.5
C6—C7—C8115.86 (14)C13—C14—H14B109.5
C2—C7—C8125.85 (14)C9—C14—H14B109.5
O2—C8—C7118.01 (14)H14A—C14—H14B108.1
O2—C8—C9120.22 (14)C16—C15—C12115.32 (15)
C7—C8—C9121.75 (14)C16—C15—H15A108.4
C8—C9—C10111.48 (13)C12—C15—H15A108.4
C8—C9—C14109.97 (13)C16—C15—H15B108.4
C10—C9—C14108.86 (13)C12—C15—H15B108.4
C8—C9—H9108.8H15A—C15—H15B107.5
C10—C9—H9108.8C15—C16—H16A109.5
C14—C9—H9108.8C15—C16—H16B109.5
C11—C10—C9109.99 (12)H16A—C16—H16B109.5
C11—C10—H10A109.7C15—C16—H16C109.5
C9—C10—H10A109.7H16A—C16—H16C109.5
C11—C10—H10B109.7H16B—C16—H16C109.5
C1—O1—C2—C35.2 (2)C2—C7—C8—C922.2 (2)
C1—O1—C2—C7177.20 (13)O2—C8—C9—C1039.5 (2)
O1—C2—C3—C4176.77 (14)C7—C8—C9—C10138.54 (14)
C7—C2—C3—C40.8 (2)O2—C8—C9—C1481.31 (18)
C2—C3—C4—C50.7 (2)C7—C8—C9—C14100.62 (16)
C3—C4—C5—C60.6 (2)C8—C9—C10—C11179.57 (13)
C3—C4—C5—Br1178.97 (11)C14—C9—C10—C1158.95 (17)
C4—C5—C6—C70.7 (2)C9—C10—C11—C1259.46 (17)
Br1—C5—C6—C7179.06 (11)C10—C11—C12—C15179.67 (13)
C5—C6—C7—C20.8 (2)C10—C11—C12—C1355.60 (18)
C5—C6—C7—C8179.56 (14)C11—C12—C13—C1453.76 (18)
O1—C2—C7—C6176.87 (13)C15—C12—C13—C14177.44 (14)
C3—C2—C7—C60.9 (2)C12—C13—C14—C956.16 (18)
O1—C2—C7—C81.7 (2)C8—C9—C14—C13179.77 (13)
C3—C2—C7—C8179.47 (14)C10—C9—C14—C1357.84 (17)
C6—C7—C8—O218.9 (2)C11—C12—C15—C16172.94 (15)
C2—C7—C8—O2159.73 (16)C13—C12—C15—C1664.1 (2)
C6—C7—C8—C9159.20 (14)

Experimental details

Crystal data
Chemical formulaC16H21BrO2
Mr325.24
Crystal system, space groupMonoclinic, P21/c
Temperature (K)113
a, b, c (Å)14.204 (3), 11.276 (2), 9.604 (2)
β (°) 102.329 (4)
V3)1502.8 (6)
Z4
Radiation typeMo Kα
µ (mm1)2.73
Crystal size (mm)0.26 × 0.22 × 0.20
Data collection
DiffractometerRigaku Saturn CCD area-detector
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku, 2007)
Tmin, Tmax0.537, 0.611
No. of measured, independent and
observed [I > 2σ(I)] reflections
13836, 3588, 2581
Rint0.033
(sin θ/λ)max1)0.658
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.024, 0.058, 1.04
No. of reflections3588
No. of parameters174
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.52, 0.28

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

 

References

First citationAllen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.  CrossRef Web of Science Google Scholar
First citationGao, Y. L., Zhao, G. L., Liu, W., Wang, Y. L., Xu, W. R. & Wang, J. W. (2010). Chin. J. Chem. 28, 605–612.  CrossRef CAS Google Scholar
First citationMeng, M., et al. (2008). J. Med. Chem. 51, 1145–1149.  Web of Science CrossRef PubMed CAS Google Scholar
First citationRigaku (2007). CrystalClear. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationShao, H., Zhao, G. L., Liu, W., Wang, Y. L., Xu, W. R. & Tang, L. D. (2010). Chin. J. Synth. Chem. 18, 389–392.  CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 5| May 2011| Page o1173
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds