(5-Bromo-2-methyl­phen­yl)(4-eth­oxy­phen­yl)methanone

Shi, Y.-H.; Zhao, G.-L.; Shao, H.; Liu, W.; Xu, W.-R.

doi:10.1107/S1600536810027327

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 8| August 2010| Page o2038

https://doi.org/10.1107/S1600536810027327

Open

access

(5-Bromo-2-methylphenyl)(4-ethoxyphenyl)methanone

Yong-Heng Shi,^a Gui-Long Zhao,^a Hua Shao,^a Wei Liu ^a and Wei-Ren Xu ^a,^b ^*

^aTianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China, and ^bSchool of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China
^*Correspondence e-mail: weirun_xu@yahoo.cn

(Received 7 July 2010; accepted 9 July 2010; online 17 July 2010)

In the title compound, C₁₆H₁₅BrO₂, the dihedral angle between the benzene rings is 68.5 (2)°. In the crystal structure, molecules are linked by weak C—H⋯O hydrogen bonds into chains parallel to the b axis.

Related literature

For details of the biological activity of SGLT2 inhibitors, see: Meng et al. (2008 ). For bond-length data, see: Allen et al. (1987 ).

Experimental

Crystal data

C₁₆H₁₅BrO₂
M_r = 319.19
Orthorhombic, P b c a
a = 9.5730 (19) Å
b = 13.188 (3) Å
c = 22.205 (4) Å
V = 2803.4 (10) Å³
Z = 8
Mo Kα radiation
μ = 2.93 mm⁻¹
T = 113 K
0.30 × 0.20 × 0.16 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ) T_min = 0.474, T_max = 0.652
17506 measured reflections
2479 independent reflections
2133 reflections with I > 2σ(I)
R_int = 0.044

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.107
S = 1.10
2479 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.84 e Å⁻³
Δρ_min = −0.57 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11⋯O1ⁱ	0.95	2.42	3.313 (3)	156
Symmetry code: (i) $[-x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]$ .

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536810027327/rz2475sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810027327/rz2475Isup2.hkl

checkCIF report

Comment top

Dapagliflozin is an anti-diabetic agent through the inhibition of renal SGLT2, which was developed by Bristol-Myers Squibb Company and is now in the phase III clinical trial (Meng et al., 2008). During the discovery of our own SGLT2 inhibitors as anti-diabetic agents, we prepared the derivatives of dapagliflozin (Meng et al., 2008) for biological evaluation, and the title compound, (5-bromo-2-methylphenyl)(4-ethoxyphenyl)methanone, was prepared as an important intermediate.

In title compound, C₁₆H₁₅BrO₂, bond lengths are normal (Allen et al., 1987)). The dihedral angle between the benzene rings (C2—C7 and C9—C14) is 68.5 (2)°. In the crystal structure, molecules interact through weak C—H···O hydrogen bonds to form chains parallel to the b axis.

Related literature top

For details of the biological activity of SGLT2 inhibitors, see: Meng et al. (2008). For bond-length data, see: Allen et al. (1987).

Experimental top

A round-bottomed flask was charged with 2.15 g (10 mmol) of 5-bromo-2-methylbenoic acid, 1 drop of DMF, 1.27 g (10 mmol) of oxalyl chloride and 3 ml of dried dichloromethane, and the mixture was stirred at room temperature over night until a clear solution formed. The reaction mixture was evaporated on a rotary evaporator to give crude 5-bromo-2-chlorobenzoyl chloride, which was dissolved in 15 ml of dried dichloromethane. The solution thus obtained was stirred while being cooled with an ice-salt bath, and 1.22 g (10 mmol) of phenetole was added followed by the addition of 1.60 g (12 mmol) of anhydrous aluminium chloride in a portionwise manner. The resulting mixture was stirred at this temperature for 1 h and poured into 150 ml of ice-water. The mixture formed was extracted with three 50 ml portions of dichloromethane, and the combined extracts were washed with 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 ethyl acetate/petroleum ether (1/5 v/v).

Structure description top

For details of the biological activity of SGLT2 inhibitors, see: Meng et al. (2008). For bond-length data, see: Allen et al. (1987).

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 40% probability level.

(5-Bromo-2-methylphenyl)(4-ethoxyphenyl)methanone top

Crystal data top

C₁₆H₁₅BrO₂	F(000) = 1296
M_r = 319.19	D_x = 1.513 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 6268 reflections
a = 9.5730 (19) Å	θ = 2.1–27.9°
b = 13.188 (3) Å	µ = 2.93 mm⁻¹
c = 22.205 (4) Å	T = 113 K
V = 2803.4 (10) Å³	Block, colorless
Z = 8	0.30 × 0.20 × 0.16 mm

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2479 independent reflections
Radiation source: rotating anode	2133 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.044
Detector resolution: 7.31 pixels mm^-1	θ_max = 25.0°, θ_min = 1.8°
ω and φ scans	h = −11→10
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	k = −15→15
T_min = 0.474, T_max = 0.652	l = −26→19
17506 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.041	H-atom parameters constrained
wR(F²) = 0.107	w = 1/[σ²(F_o²) + (0.0598P)² + 1.3319P] where P = (F_o² + 2F_c²)/3
S = 1.10	(Δ/σ)_max = 0.004
2479 reflections	Δρ_max = 0.84 e Å⁻³
175 parameters	Δρ_min = −0.57 e Å⁻³
0 restraints	Extinction correction: SHELXTL (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0120 (8)

Crystal data top

C₁₆H₁₅BrO₂	V = 2803.4 (10) Å³
M_r = 319.19	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 9.5730 (19) Å	µ = 2.93 mm⁻¹
b = 13.188 (3) Å	T = 113 K
c = 22.205 (4) Å	0.30 × 0.20 × 0.16 mm

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2479 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	2133 reflections with I > 2σ(I)
T_min = 0.474, T_max = 0.652	R_int = 0.044
17506 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.107	H-atom parameters constrained
S = 1.10	Δρ_max = 0.84 e Å⁻³
2479 reflections	Δρ_min = −0.57 e Å⁻³
175 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	−0.00393 (3)	0.34535 (2)	0.307507 (13)	0.03274 (18)
O1	0.0807 (2)	0.03567 (15)	0.10091 (9)	0.0353 (5)
O2	0.1222 (2)	0.43270 (15)	−0.05895 (8)	0.0322 (5)
C1	0.3438 (3)	0.0117 (2)	0.18087 (13)	0.0354 (7)
H1A	0.4351	0.0104	0.2009	0.053*
H1B	0.3562	0.0299	0.1384	0.053*
H1C	0.3005	−0.0555	0.1836	0.053*
C2	0.2512 (3)	0.08893 (19)	0.21113 (13)	0.0259 (6)
C3	0.2670 (3)	0.1078 (2)	0.27228 (13)	0.0286 (6)
H3	0.3328	0.0691	0.2946	0.034*
C4	0.1895 (3)	0.1816 (2)	0.30181 (12)	0.0303 (7)
H4	0.1999	0.1921	0.3439	0.036*
C5	0.0968 (3)	0.2395 (2)	0.26867 (11)	0.0269 (6)
C6	0.0771 (3)	0.2229 (2)	0.20780 (12)	0.0264 (6)
H6	0.0129	0.2633	0.1857	0.032*
C7	0.1528 (3)	0.1459 (2)	0.17905 (12)	0.0255 (6)
C8	0.1169 (3)	0.1222 (2)	0.11452 (12)	0.0267 (6)
C9	0.1212 (3)	0.2048 (2)	0.06972 (11)	0.0246 (6)
C10	0.2006 (3)	0.2915 (2)	0.07938 (11)	0.0256 (6)
H10	0.2518	0.2979	0.1158	0.031*
C11	0.2069 (3)	0.3687 (2)	0.03726 (11)	0.0250 (6)
H11	0.2634	0.4268	0.0442	0.030*
C12	0.1289 (3)	0.3597 (2)	−0.01543 (12)	0.0267 (6)
C13	0.0496 (3)	0.2727 (2)	−0.02606 (12)	0.0308 (7)
H13	−0.0032	0.2668	−0.0621	0.037*
C14	0.0480 (3)	0.1956 (2)	0.01559 (12)	0.0294 (6)
H14	−0.0034	0.1356	0.0075	0.035*
C15	0.2006 (3)	0.5248 (2)	−0.04965 (13)	0.0334 (7)
H15A	0.3020	0.5102	−0.0497	0.040*
H15B	0.1756	0.5557	−0.0105	0.040*
C16	0.1645 (3)	0.5955 (2)	−0.10032 (13)	0.0364 (7)
H16A	0.1906	0.5644	−0.1388	0.055*
H16B	0.2154	0.6594	−0.0952	0.055*
H16C	0.0638	0.6090	−0.1000	0.055*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0346 (3)	0.0327 (3)	0.0309 (3)	0.00282 (11)	0.01170 (11)	−0.00058 (11)
O1	0.0412 (13)	0.0268 (11)	0.0379 (11)	−0.0026 (9)	−0.0050 (9)	−0.0040 (8)
O2	0.0373 (12)	0.0317 (12)	0.0276 (10)	−0.0050 (9)	−0.0020 (8)	0.0032 (8)
C1	0.0350 (17)	0.0322 (18)	0.0390 (16)	0.0046 (14)	−0.0043 (13)	−0.0038 (13)
C2	0.0237 (15)	0.0226 (15)	0.0314 (15)	−0.0026 (12)	−0.0001 (11)	0.0005 (11)
C3	0.0281 (16)	0.0264 (16)	0.0314 (15)	0.0010 (12)	−0.0050 (11)	0.0036 (11)
C4	0.0317 (16)	0.0343 (16)	0.0248 (14)	−0.0063 (13)	0.0020 (11)	0.0019 (11)
C5	0.0265 (15)	0.0269 (15)	0.0273 (14)	−0.0050 (12)	0.0061 (11)	0.0013 (11)
C6	0.0209 (14)	0.0275 (15)	0.0307 (14)	0.0008 (11)	0.0022 (11)	0.0026 (11)
C7	0.0225 (15)	0.0246 (16)	0.0293 (14)	−0.0032 (11)	−0.0001 (11)	−0.0010 (10)
C8	0.0180 (14)	0.0304 (16)	0.0318 (15)	0.0022 (11)	0.0000 (10)	−0.0044 (13)
C9	0.0207 (14)	0.0278 (15)	0.0254 (14)	0.0031 (11)	−0.0018 (10)	−0.0037 (11)
C10	0.0197 (14)	0.0326 (16)	0.0245 (13)	0.0032 (12)	−0.0018 (10)	−0.0054 (11)
C11	0.0199 (14)	0.0273 (14)	0.0278 (14)	−0.0022 (11)	0.0023 (10)	−0.0060 (11)
C12	0.0245 (15)	0.0302 (16)	0.0254 (14)	0.0011 (12)	0.0029 (11)	0.0004 (11)
C13	0.0298 (16)	0.0361 (18)	0.0266 (15)	−0.0041 (13)	−0.0052 (12)	−0.0055 (12)
C14	0.0253 (15)	0.0309 (16)	0.0321 (16)	−0.0037 (13)	−0.0017 (12)	−0.0033 (12)
C15	0.0311 (16)	0.0324 (17)	0.0367 (16)	−0.0045 (13)	0.0001 (12)	0.0007 (12)
C16	0.0335 (17)	0.0361 (18)	0.0397 (16)	−0.0011 (13)	0.0051 (13)	0.0063 (13)

Geometric parameters (Å, º) top

Br1—C5	1.903 (3)	C8—C9	1.475 (4)
O1—C8	1.230 (3)	C9—C10	1.389 (4)
O2—C12	1.365 (3)	C9—C14	1.397 (4)
O2—C15	1.442 (3)	C10—C11	1.385 (4)
C1—C2	1.509 (4)	C10—H10	0.9500
C1—H1A	0.9800	C11—C12	1.393 (4)
C1—H1B	0.9800	C11—H11	0.9500
C1—H1C	0.9800	C12—C13	1.396 (4)
C2—C3	1.389 (4)	C13—C14	1.374 (4)
C2—C7	1.400 (4)	C13—H13	0.9500
C3—C4	1.388 (4)	C14—H14	0.9500
C3—H3	0.9500	C15—C16	1.502 (4)
C4—C5	1.382 (4)	C15—H15A	0.9900
C4—H4	0.9500	C15—H15B	0.9900
C5—C6	1.382 (4)	C16—H16A	0.9800
C6—C7	1.401 (4)	C16—H16B	0.9800
C6—H6	0.9500	C16—H16C	0.9800
C7—C8	1.506 (4)

C12—O2—C15	117.9 (2)	C10—C9—C8	121.2 (2)
C2—C1—H1A	109.5	C14—C9—C8	120.2 (2)
C2—C1—H1B	109.5	C11—C10—C9	121.7 (2)
H1A—C1—H1B	109.5	C11—C10—H10	119.2
C2—C1—H1C	109.5	C9—C10—H10	119.2
H1A—C1—H1C	109.5	C10—C11—C12	118.8 (3)
H1B—C1—H1C	109.5	C10—C11—H11	120.6
C3—C2—C7	118.3 (2)	C12—C11—H11	120.6
C3—C2—C1	119.5 (2)	O2—C12—C11	124.0 (2)
C7—C2—C1	122.1 (3)	O2—C12—C13	115.7 (2)
C2—C3—C4	122.0 (3)	C11—C12—C13	120.2 (2)
C2—C3—H3	119.0	C14—C13—C12	120.0 (3)
C4—C3—H3	119.0	C14—C13—H13	120.0
C5—C4—C3	118.6 (2)	C12—C13—H13	120.0
C5—C4—H4	120.7	C13—C14—C9	120.6 (3)
C3—C4—H4	120.7	C13—C14—H14	119.7
C6—C5—C4	121.4 (3)	C9—C14—H14	119.7
C6—C5—Br1	119.3 (2)	O2—C15—C16	107.2 (2)
C4—C5—Br1	119.3 (2)	O2—C15—H15A	110.3
C5—C6—C7	119.3 (3)	C16—C15—H15A	110.3
C5—C6—H6	120.4	O2—C15—H15B	110.3
C7—C6—H6	120.4	C16—C15—H15B	110.3
C2—C7—C6	120.4 (3)	H15A—C15—H15B	108.5
C2—C7—C8	121.7 (2)	C15—C16—H16A	109.5
C6—C7—C8	117.8 (2)	C15—C16—H16B	109.5
O1—C8—C9	121.8 (2)	H16A—C16—H16B	109.5
O1—C8—C7	119.4 (2)	C15—C16—H16C	109.5
C9—C8—C7	118.8 (2)	H16A—C16—H16C	109.5
C10—C9—C14	118.6 (3)	H16B—C16—H16C	109.5

C7—C2—C3—C4	−0.7 (4)	O1—C8—C9—C10	−159.8 (3)
C1—C2—C3—C4	176.7 (3)	C7—C8—C9—C10	22.6 (4)
C2—C3—C4—C5	−1.8 (4)	O1—C8—C9—C14	18.3 (4)
C3—C4—C5—C6	2.2 (4)	C7—C8—C9—C14	−159.3 (3)
C3—C4—C5—Br1	−177.0 (2)	C14—C9—C10—C11	0.9 (4)
C4—C5—C6—C7	−0.1 (4)	C8—C9—C10—C11	179.0 (2)
Br1—C5—C6—C7	179.1 (2)	C9—C10—C11—C12	1.5 (4)
C3—C2—C7—C6	2.8 (4)	C15—O2—C12—C11	−0.1 (4)
C1—C2—C7—C6	−174.6 (3)	C15—O2—C12—C13	179.1 (2)
C3—C2—C7—C8	−172.7 (2)	C10—C11—C12—O2	177.1 (2)
C1—C2—C7—C8	10.0 (4)	C10—C11—C12—C13	−2.0 (4)
C5—C6—C7—C2	−2.4 (4)	O2—C12—C13—C14	−179.0 (3)
C5—C6—C7—C8	173.2 (2)	C11—C12—C13—C14	0.2 (4)
C2—C7—C8—O1	53.5 (4)	C12—C13—C14—C9	2.2 (4)
C6—C7—C8—O1	−122.1 (3)	C10—C9—C14—C13	−2.8 (4)
C2—C7—C8—C9	−128.8 (3)	C8—C9—C14—C13	179.1 (3)
C6—C7—C8—C9	55.6 (3)	C12—O2—C15—C16	−174.5 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11···O1ⁱ	0.95	2.42	3.313 (3)	156

Symmetry code: (i) −x+1/2, y+1/2, z.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₅BrO₂
M_r	319.19
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	113
a, b, c (Å)	9.5730 (19), 13.188 (3), 22.205 (4)
V (Å³)	2803.4 (10)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	2.93
Crystal size (mm)	0.30 × 0.20 × 0.16

Data collection
Diffractometer	Rigaku Saturn CCD area-detector
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2005)
T_min, T_max	0.474, 0.652
No. of measured, independent and observed [I > 2σ(I)] reflections	17506, 2479, 2133
R_int	0.044
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.107, 1.10
No. of reflections	2479
No. of parameters	175
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.84, −0.57

Computer programs: CrystalClear (Rigaku, 2005), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11···O1ⁱ	0.95	2.42	3.313 (3)	155.8

Symmetry code: (i) −x+1/2, y+1/2, z.

References

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. CSD CrossRef Web of Science Google Scholar
Meng, M., Ellsworth, B. A., Nirschl, A. A., McCann, P. J., Patel, M., Girotra, R. N., Wu, G., Sher, P. M., Morrison, E. P., Biller, S. A., Zahler, R., Deshpande, P. P., Pullockaran, A., Hagan, D. L., Morgan, N., Taylor, J. R., Obermeier, M. T., Humphreys, W. G., Khanna, A., Discenza, L., Robertson, J. M., Wang, A., Han, S., Wetterau, J. R., Janovitz, E. B., Flint, O. P., Whaley, J. M. & Washburn, W. N. (2008). J. Med. Chem. 51, 1145–1149. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku. (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, 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.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 8| August 2010| Page o2038

https://doi.org/10.1107/S1600536810027327

Open

access