4-Bromo-2-[1-(4-eth­oxy­phen­yl)-1-methyl­eth­yl]-1-methyl­benzene

Li, Y.; Kong, X.; Chen, G.-H.; Chi, J.-G.; Wang, J.-N.

doi:10.1107/S1600536810049445

organic compounds

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ISSN: 2056-9890

Volume 67| Part 1| January 2011| Page o21

https://doi.org/10.1107/S1600536810049445

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4-Bromo-2-[1-(4-ethoxyphenyl)-1-methylethyl]-1-methylbenzene

Yan Li,^a Xue Kong,^a Guan-Hong Chen,^a Jian-Guo Chi ^a and Jia-Ning Wang ^a ^*

^aBiology Institute of Shandong Academy of Sciences, Jinan 250014, People's Republic of China
^*Correspondence e-mail: wangjianning2010@yahoo.cn

(Received 25 November 2010; accepted 26 November 2010; online 4 December 2010)

In title compound, C₁₈H₂₁BrO, the dihedral angle between two rings is 85.72°. No classical hydrogen bonds are found and only van der Waals forces stabilize the crystal packing.

Related literature

For details of the biological activity of SGLT2 inhibitors, a class of promising anti-hyperglycemic agents, see: Meng et al. (2008 ); Gao et al. (2010a ,b ). For bond-length data, see: Allen et al. (1987 ).

Experimental

Crystal data

C₁₈H₂₁BrO
M_r = 333.26
Monoclinic, P 2₁ /n
a = 11.164 (2) Å
b = 9.5142 (19) Å
c = 16.135 (3) Å
β = 110.21 (3)°
V = 1608.2 (6) Å³
Z = 4
Mo Kα radiation
μ = 2.55 mm⁻¹
T = 293 K
0.20 × 0.16 × 0.08 mm

Data collection

Rigaku Saturn diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ) T_min = 0.630, T_max = 0.822
13056 measured reflections
2839 independent reflections
2101 reflections with I > 2σ(I)
R_int = 0.054

Refinement

R[F² > 2σ(F²)] = 0.051
wR(F²) = 0.130
S = 1.05
2839 reflections
186 parameters
H-atom parameters constrained
Δρ_max = 0.52 e Å⁻³
Δρ_min = −0.39 e Å⁻³

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/S1600536810049445/hg2759sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810049445/hg2759Isup2.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., 2010a,b).

In title compound, C₁₈H₂₁BrO, bond lengths are normal (Allen et al., 1987). The dihedral angle between two phenyl ring (C2—C7 and C11—C16) is 85.72 °. No classic hydrogen bonds found, only Van der Waals forces stabilize the crystal packing.

Related literature top

For details of the biological activity of SGLT2 inhibitors, a class of promising anti-hyperglycemic agents, see: Meng et al. (2008); Gao et al. (2010a,b). For bond-b,length data, see: Allen et al. (1987).

Experimental top

A dried 100-ml round-bottomed flask was charged with 2.29 g (10 mmol) of 1-(5-bromo-2-methylphenyl)-1-methylethanol, 1.22 g (10 mmol) of phenetol and 15 ml of dried dichloromethane, and the clear solution thus obtained was stirred on an ice bath followed by addition of 1.33 g (10 mmol) of anhydrous aluminium chloride in a portionwise manner. After addition, the reaction mixture was stirred at room temperature for another one hour when TLC analysis indicated that all the starting materials were consumed completely. The reaction mixture was poured into 300 ml of ice-water and exacted with three 50-ml portions of dichloromethane, and the combined exacts were washed with saturated brine, dried over sodium sulfate and evaporated on a rotary evaporator to afford the crude product as a colorless oil, which was purified by column chromatography to yield the pure product as colorless crystals. Single crystals suitable for X-ray diffraction were obtained from slow evaporation of a solution of the pure title compound in dichloromethane/petroleum ether (1/4) at room temperature.

Structure description top

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. View of the title compound, with displacement ellipsoids drawn at the 40% probability level.

4-Bromo-2-[1-(4-ethoxyphenyl)-1-methylethyl]-1-methylbenzene top

Crystal data top

C₁₈H₂₁BrO	F(000) = 688
M_r = 333.26	D_x = 1.376 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3726 reflections
a = 11.164 (2) Å	θ = 2.1–27.1°
b = 9.5142 (19) Å	µ = 2.55 mm⁻¹
c = 16.135 (3) Å	T = 293 K
β = 110.21 (3)°	Prism, colorless
V = 1608.2 (6) Å³	0.20 × 0.16 × 0.08 mm
Z = 4

Data collection top

Rigaku Saturn diffractometer	2839 independent reflections
Radiation source: rotating anode	2101 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.054
ω scans	θ_max = 25.0°, θ_min = 1.9°
Absorption correction: multi-scan (CystalClear; Rigaku, 2005)	h = −13→12
T_min = 0.630, T_max = 0.822	k = −11→11
13056 measured reflections	l = −17→19

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)] = 0.051	H-atom parameters constrained
wR(F²) = 0.130	w = 1/[σ²(F_o²) + (0.070P)²] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.001
2839 reflections	Δρ_max = 0.52 e Å⁻³
186 parameters	Δρ_min = −0.39 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: 0.026 (2)

Crystal data top

C₁₈H₂₁BrO	V = 1608.2 (6) Å³
M_r = 333.26	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 11.164 (2) Å	µ = 2.55 mm⁻¹
b = 9.5142 (19) Å	T = 293 K
c = 16.135 (3) Å	0.20 × 0.16 × 0.08 mm
β = 110.21 (3)°

Data collection top

Rigaku Saturn diffractometer	2839 independent reflections
Absorption correction: multi-scan (CystalClear; Rigaku, 2005)	2101 reflections with I > 2σ(I)
T_min = 0.630, T_max = 0.822	R_int = 0.054
13056 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.051	0 restraints
wR(F²) = 0.130	H-atom parameters constrained
S = 1.05	Δρ_max = 0.52 e Å⁻³
2839 reflections	Δρ_min = −0.39 e Å⁻³
186 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	0.02586 (4)	0.72212 (4)	0.15240 (3)	0.0665 (3)
O1	0.1869 (3)	−0.2600 (3)	0.39327 (19)	0.0644 (8)
C1	−0.1877 (4)	0.1214 (4)	0.1522 (3)	0.0751 (13)
H1A	−0.2276	0.0963	0.0912	0.113*
H1B	−0.2496	0.1180	0.1812	0.113*
H1C	−0.1198	0.0566	0.1802	0.113*
C2	−0.1338 (4)	0.2691 (4)	0.1586 (3)	0.0545 (10)
C3	−0.1463 (4)	0.3354 (5)	0.0805 (3)	0.0647 (11)
H3	−0.1872	0.2878	0.0279	0.078*
C4	−0.1010 (4)	0.4700 (4)	0.0762 (3)	0.0635 (11)
H4	−0.1120	0.5129	0.0222	0.076*
C5	−0.0388 (3)	0.5377 (4)	0.1551 (2)	0.0497 (9)
C6	−0.0249 (3)	0.4749 (4)	0.2352 (2)	0.0491 (9)
H6	0.0166	0.5236	0.2872	0.059*
C7	−0.0716 (3)	0.3405 (4)	0.2397 (2)	0.0467 (8)
C8	−0.0623 (4)	0.2769 (4)	0.3297 (3)	0.0501 (9)
C9	−0.1980 (4)	0.2698 (4)	0.3348 (3)	0.0736 (13)
H9A	−0.2450	0.1953	0.2975	0.110*
H9B	−0.2410	0.3575	0.3153	0.110*
H9C	−0.1921	0.2522	0.3946	0.110*
C10	0.0203 (4)	0.3690 (4)	0.4079 (3)	0.0723 (12)
H10A	0.0296	0.3226	0.4626	0.108*
H10B	−0.0206	0.4583	0.4062	0.108*
H10C	0.1029	0.3831	0.4034	0.108*
C11	0.0025 (3)	0.1309 (4)	0.3436 (2)	0.0471 (9)
C12	−0.0460 (4)	0.0150 (4)	0.3738 (2)	0.0575 (10)
H12	−0.1226	0.0235	0.3843	0.069*
C13	0.0171 (4)	−0.1130 (4)	0.3887 (3)	0.0628 (11)
H13	−0.0187	−0.1895	0.4075	0.075*
C14	0.1324 (4)	−0.1283 (4)	0.3759 (2)	0.0513 (9)
C15	0.1832 (3)	−0.0141 (4)	0.3464 (2)	0.0525 (9)
H15	0.2603	−0.0225	0.3367	0.063*
C16	0.1182 (3)	0.1130 (4)	0.3314 (2)	0.0543 (10)
H16	0.1539	0.1893	0.3123	0.065*
C17	0.3065 (4)	−0.2787 (4)	0.3818 (3)	0.0673 (12)
H17A	0.3699	−0.2168	0.4211	0.081*
H17B	0.2990	−0.2568	0.3215	0.081*
C18	0.3460 (4)	−0.4312 (5)	0.4026 (3)	0.0896 (15)
H18A	0.3480	−0.4533	0.4611	0.134*
H18B	0.4292	−0.4454	0.3991	0.134*
H18C	0.2856	−0.4913	0.3608	0.134*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0704 (4)	0.0471 (3)	0.0812 (4)	−0.00704 (19)	0.0251 (3)	0.01185 (19)
O1	0.068 (2)	0.0553 (17)	0.076 (2)	0.0164 (13)	0.0322 (16)	0.0155 (13)
C1	0.086 (3)	0.056 (3)	0.068 (3)	−0.020 (2)	0.009 (2)	−0.001 (2)
C2	0.054 (2)	0.042 (2)	0.055 (2)	−0.0056 (17)	0.004 (2)	0.0034 (17)
C3	0.068 (3)	0.055 (2)	0.056 (2)	−0.009 (2)	0.003 (2)	0.000 (2)
C4	0.063 (3)	0.065 (3)	0.054 (2)	0.001 (2)	0.008 (2)	0.012 (2)
C5	0.044 (2)	0.044 (2)	0.061 (2)	−0.0016 (16)	0.0181 (18)	0.0061 (17)
C6	0.050 (2)	0.046 (2)	0.050 (2)	−0.0002 (17)	0.0151 (17)	0.0002 (16)
C7	0.0421 (19)	0.039 (2)	0.058 (2)	−0.0014 (16)	0.0158 (17)	0.0028 (17)
C8	0.057 (2)	0.041 (2)	0.058 (2)	0.0041 (17)	0.0268 (19)	0.0062 (16)
C9	0.079 (3)	0.053 (3)	0.109 (4)	0.014 (2)	0.057 (3)	0.015 (2)
C10	0.114 (4)	0.054 (3)	0.053 (2)	−0.003 (2)	0.034 (2)	−0.0004 (19)
C11	0.053 (2)	0.042 (2)	0.047 (2)	−0.0014 (17)	0.0175 (17)	0.0036 (15)
C12	0.061 (2)	0.048 (2)	0.073 (3)	0.0085 (19)	0.037 (2)	0.0136 (19)
C13	0.072 (3)	0.046 (2)	0.080 (3)	0.006 (2)	0.037 (2)	0.018 (2)
C14	0.058 (2)	0.049 (2)	0.045 (2)	0.0076 (18)	0.0151 (18)	0.0053 (16)
C15	0.043 (2)	0.056 (2)	0.059 (2)	0.0039 (18)	0.0194 (18)	0.0040 (18)
C16	0.053 (2)	0.051 (2)	0.057 (2)	−0.0035 (18)	0.0159 (19)	0.0081 (17)
C17	0.066 (3)	0.059 (3)	0.073 (3)	0.009 (2)	0.020 (2)	−0.001 (2)
C18	0.082 (3)	0.064 (3)	0.120 (4)	0.024 (2)	0.032 (3)	0.007 (3)

Geometric parameters (Å, º) top

Br1—C5	1.904 (4)	C9—H9B	0.9600
O1—C14	1.379 (4)	C9—H9C	0.9600
O1—C17	1.421 (6)	C10—H10A	0.9600
C1—C2	1.518 (5)	C10—H10B	0.9600
C1—H1A	0.9600	C10—H10C	0.9600
C1—H1B	0.9600	C11—C16	1.384 (5)
C1—H1C	0.9600	C11—C12	1.389 (5)
C2—C3	1.373 (5)	C12—C13	1.386 (5)
C2—C7	1.423 (5)	C12—H12	0.9300
C3—C4	1.388 (6)	C13—C14	1.380 (5)
C3—H3	0.9300	C13—H13	0.9300
C4—C5	1.381 (5)	C14—C15	1.385 (5)
C4—H4	0.9300	C15—C16	1.388 (5)
C5—C6	1.382 (5)	C15—H15	0.9300
C6—C7	1.393 (5)	C16—H16	0.9300
C6—H6	0.9300	C17—C18	1.520 (5)
C7—C8	1.543 (5)	C17—H17A	0.9700
C8—C11	1.545 (5)	C17—H17B	0.9700
C8—C9	1.546 (6)	C18—H18A	0.9600
C8—C10	1.552 (6)	C18—H18B	0.9600
C9—H9A	0.9600	C18—H18C	0.9600

C14—O1—C17	117.1 (3)	C8—C10—H10A	109.5
C2—C1—H1A	109.5	C8—C10—H10B	109.5
C2—C1—H1B	109.5	H10A—C10—H10B	109.5
H1A—C1—H1B	109.5	C8—C10—H10C	109.5
C2—C1—H1C	109.5	H10A—C10—H10C	109.5
H1A—C1—H1C	109.5	H10B—C10—H10C	109.5
H1B—C1—H1C	109.5	C16—C11—C12	116.7 (3)
C3—C2—C7	119.2 (3)	C16—C11—C8	120.2 (3)
C3—C2—C1	116.8 (3)	C12—C11—C8	123.0 (3)
C7—C2—C1	124.1 (3)	C13—C12—C11	121.5 (3)
C2—C3—C4	123.2 (4)	C13—C12—H12	119.3
C2—C3—H3	118.4	C11—C12—H12	119.3
C4—C3—H3	118.4	C14—C13—C12	120.8 (4)
C5—C4—C3	117.4 (3)	C14—C13—H13	119.6
C5—C4—H4	121.3	C12—C13—H13	119.6
C3—C4—H4	121.3	O1—C14—C13	115.8 (3)
C4—C5—C6	121.3 (3)	O1—C14—C15	125.4 (3)
C4—C5—Br1	118.8 (3)	C13—C14—C15	118.9 (3)
C6—C5—Br1	119.9 (3)	C14—C15—C16	119.5 (3)
C5—C6—C7	121.5 (3)	C14—C15—H15	120.3
C5—C6—H6	119.3	C16—C15—H15	120.3
C7—C6—H6	119.3	C11—C16—C15	122.7 (3)
C6—C7—C2	117.6 (3)	C11—C16—H16	118.6
C6—C7—C8	120.3 (3)	C15—C16—H16	118.6
C2—C7—C8	122.0 (3)	O1—C17—C18	107.7 (4)
C7—C8—C11	111.5 (3)	O1—C17—H17A	110.2
C7—C8—C9	108.5 (3)	C18—C17—H17A	110.2
C11—C8—C9	111.8 (3)	O1—C17—H17B	110.2
C7—C8—C10	111.8 (3)	C18—C17—H17B	110.2
C11—C8—C10	105.8 (3)	H17A—C17—H17B	108.5
C9—C8—C10	107.4 (3)	C17—C18—H18A	109.5
C8—C9—H9A	109.5	C17—C18—H18B	109.5
C8—C9—H9B	109.5	H18A—C18—H18B	109.5
H9A—C9—H9B	109.5	C17—C18—H18C	109.5
C8—C9—H9C	109.5	H18A—C18—H18C	109.5
H9A—C9—H9C	109.5	H18B—C18—H18C	109.5
H9B—C9—H9C	109.5

C7—C2—C3—C4	0.1 (6)	C7—C8—C11—C16	50.9 (5)
C1—C2—C3—C4	−179.6 (4)	C9—C8—C11—C16	172.5 (4)
C2—C3—C4—C5	1.0 (6)	C10—C8—C11—C16	−70.9 (4)
C3—C4—C5—C6	−1.4 (6)	C7—C8—C11—C12	−133.2 (4)
C3—C4—C5—Br1	179.7 (3)	C9—C8—C11—C12	−11.6 (5)
C4—C5—C6—C7	0.7 (5)	C10—C8—C11—C12	105.0 (4)
Br1—C5—C6—C7	179.6 (3)	C16—C11—C12—C13	−1.6 (6)
C5—C6—C7—C2	0.4 (5)	C8—C11—C12—C13	−177.6 (4)
C5—C6—C7—C8	−176.1 (3)	C11—C12—C13—C14	1.6 (6)
C3—C2—C7—C6	−0.8 (6)	C17—O1—C14—C13	−179.2 (4)
C1—C2—C7—C6	178.8 (4)	C17—O1—C14—C15	1.6 (5)
C3—C2—C7—C8	175.7 (4)	C12—C13—C14—O1	179.6 (4)
C1—C2—C7—C8	−4.7 (6)	C12—C13—C14—C15	−1.2 (6)
C6—C7—C8—C11	−127.0 (4)	O1—C14—C15—C16	179.9 (3)
C2—C7—C8—C11	56.7 (5)	C13—C14—C15—C16	0.8 (5)
C6—C7—C8—C9	109.5 (4)	C12—C11—C16—C15	1.2 (5)
C2—C7—C8—C9	−66.8 (4)	C8—C11—C16—C15	177.3 (3)
C6—C7—C8—C10	−8.8 (5)	C14—C15—C16—C11	−0.8 (6)
C2—C7—C8—C10	174.9 (4)	C14—O1—C17—C18	−178.8 (3)

Experimental details

Crystal data
Chemical formula	C₁₈H₂₁BrO
M_r	333.26
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	11.164 (2), 9.5142 (19), 16.135 (3)
β (°)	110.21 (3)
V (Å³)	1608.2 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	2.55
Crystal size (mm)	0.20 × 0.16 × 0.08

Data collection
Diffractometer	Rigaku Saturn
Absorption correction	Multi-scan (CystalClear; Rigaku, 2005)
T_min, T_max	0.630, 0.822
No. of measured, independent and observed [I > 2σ(I)] reflections	13056, 2839, 2101
R_int	0.054
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.051, 0.130, 1.05
No. of reflections	2839
No. of parameters	186
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.52, −0.39

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

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
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