4-(4-Fluoro­phen­yl)-1-methoxy­methyl-2-phenyl-1H-imidazole

Selig, R.; Schollmeyer, D.; Albrecht, W.; Laufer, S.

doi:10.1107/S1600536809042366

organic compounds

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ISSN: 2056-9890

Volume 65| Part 11| November 2009| Page o2803

https://doi.org/10.1107/S1600536809042366

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4-(4-Fluorophenyl)-1-methoxymethyl-2-phenyl-1H-imidazole

Roland Selig,^a ^* Dieter Schollmeyer,^b Wolfgang Albrecht ^c and Stefan Laufer ^a

^aEberhard-Karls-University Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany, ^bUniversity Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany, and ^cc-a-i-r biosciences GmbH, Paul-Ehrlich-Strasse 15, 72076 Tübingen, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 14 October 2009; accepted 15 October 2009; online 23 October 2009)

In the crystal structure of the title compound, C₁₇H₁₅FN₂O, the molecules form a three-dimensional network stabilized by π–π interactions between two imidazole rings related by a centre of symmetry. The distance between the centroids is 3.5488 (8) Å. The imidazole ring makes dihedral angles of 14.30 (7) and 33.39 (7)° with the 4-fluorophenyl ring and the phenyl ring, respectively.

Related literature

For the preparation of diarylimidazoles, see: Li et al. (2002 ). For synthesis of and with related diarylimidazoles, see: Liverton et al. (1999 ); Kawasaki et al. (1996 ).

Experimental

Crystal data

C₁₇H₁₅FN₂O
M_r = 282.31
Monoclinic, P 2₁ /n
a = 10.524 (1) Å
b = 11.248 (1) Å
c = 11.981 (1) Å
β = 92.206 (3)°
V = 1417.2 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.40 × 0.30 × 0.10 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: none
37183 measured reflections
3319 independent reflections
2745 reflections with I > 2σ(I)
R_int = 0.043

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.106
S = 1.07
3319 reflections
191 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536809042366/bt5098sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809042366/bt5098Isup2.hkl

checkCIF report

Comment top

Metallated imidazole intermediates can be widely used in the preparation of imidazole derivatives. To avoid N-metallation, N-protection of the imidazole is necessary. Our approach was a direct regioselective N-protection of the diarylimidazole. The regioselectivity is controlled by the steric effect of the aryl substituent in C-4 position. The title compound forms a three dimensional network stabilized by π-π interactions between two symmetry related imidazole nuclei. The distance between the centroids is 3.5488 (8) Å. The imidazole ring makes dihedral angles of 14.30 (7)° and 33.39 (7)° to the 4-fluorophenyl ring and the phenyl ring, respectively.

Related literature top

For the preparation of diarylimidazoles, see: Li et al. (2002). For related literature [on what subject?], see: Liverton et al. (1999); Kawasaki et al. (1996).

Experimental top

4-(4-fluorophenyl)-2-phenyl-1H-imidazole (3 g 13 mmol) was dissolved in dry THF (30 ml). After cooling to 273 K sodium bis(trimetyl silyl)amide (8.2 ml, 16 mmol) was added dropwise. The reaction mixture was stirred for 30 min at this temperature. Methoxymethylchloride (2.1M in toluene) (12 ml, 25 mmol) was added dropwise. Stirring was continued at 273 K for 30 min and further 60 min at room temperature. Then concentrated aqueous ammonium chloride solution (30 ml) was added, the reaction mixture was stirred for 1 h. After extraction with ethyl acetate the organic layer was washed twice with water, dried over sodium sulfate and evaporated under reduced pressure. The crude product was purified by flash chromatography to yield 4-(4-fluorophenyl)-1-(methoxymethyl)-2-phenyl-1H-imidazole (42%).

Structure description top

For the preparation of diarylimidazoles, see: Li et al. (2002). For related literature [on what subject?], see: Liverton et al. (1999); Kawasaki et al. (1996).

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top

Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

4-(4-Fluorophenyl)-1-methoxymethyl-2-phenyl-1H-imidazole top

Crystal data top

C₁₇H₁₅FN₂O	F(000) = 592
M_r = 282.31	D_x = 1.323 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2yn	Cell parameters from 9878 reflections
a = 10.524 (1) Å	θ = 2.4–27.6°
b = 11.2480 (11) Å	µ = 0.09 mm⁻¹
c = 11.9810 (12) Å	T = 173 K
β = 92.206 (3)°	Needle, colourless
V = 1417.2 (2) Å³	0.40 × 0.30 × 0.10 mm
Z = 4

Data collection top

Bruker SMART CCD diffractometer	2745 reflections with I > 2σ(I)
Radiation source: sealed Tube	R_int = 0.043
Graphite monochromator	θ_max = 27.7°, θ_min = 2.5°
CCD scan	h = −13→13
37183 measured reflections	k = −14→14
3319 independent reflections	l = −15→15

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.106	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0415P)² + 0.5423P] where P = (F_o² + 2F_c²)/3
3319 reflections	(Δ/σ)_max = 0.001
191 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₇H₁₅FN₂O	V = 1417.2 (2) Å³
M_r = 282.31	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 10.524 (1) Å	µ = 0.09 mm⁻¹
b = 11.2480 (11) Å	T = 173 K
c = 11.9810 (12) Å	0.40 × 0.30 × 0.10 mm
β = 92.206 (3)°

Data collection top

Bruker SMART CCD diffractometer	2745 reflections with I > 2σ(I)
37183 measured reflections	R_int = 0.043
3319 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.106	H-atom parameters constrained
S = 1.07	Δρ_max = 0.28 e Å⁻³
3319 reflections	Δρ_min = −0.18 e Å⁻³
191 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
C1	0.37469 (12)	0.48140 (11)	0.36743 (10)	0.0272 (3)
N2	0.47445 (10)	0.45452 (9)	0.30842 (8)	0.0284 (2)
C3	0.55709 (12)	0.54982 (10)	0.32055 (10)	0.0268 (3)
C4	0.50522 (12)	0.63404 (11)	0.38760 (10)	0.0289 (3)
H4	0.5423	0.7079	0.4093	0.035*
N5	0.38931 (10)	0.59103 (9)	0.41746 (8)	0.0281 (2)
C6	0.26578 (12)	0.40118 (11)	0.38101 (10)	0.0282 (3)
C7	0.14177 (12)	0.44168 (12)	0.39029 (11)	0.0348 (3)
H7	0.1246	0.5246	0.3893	0.042*
C8	0.04297 (14)	0.36122 (14)	0.40103 (13)	0.0414 (3)
H8	−0.0413	0.3896	0.4082	0.050*
C9	0.06605 (14)	0.23974 (14)	0.40139 (12)	0.0424 (3)
H9	−0.0019	0.1852	0.4097	0.051*
C10	0.18894 (14)	0.19848 (13)	0.38951 (12)	0.0390 (3)
H10	0.2051	0.1154	0.3879	0.047*
C11	0.28813 (13)	0.27826 (11)	0.37999 (11)	0.0323 (3)
H11	0.3723	0.2494	0.3727	0.039*
C12	0.68112 (12)	0.55033 (10)	0.26877 (10)	0.0270 (3)
C13	0.70870 (13)	0.46715 (11)	0.18610 (11)	0.0318 (3)
H13	0.6454	0.4118	0.1618	0.038*
C14	0.82693 (13)	0.46451 (11)	0.13935 (11)	0.0342 (3)
H14	0.8453	0.4076	0.0837	0.041*
C15	0.91715 (13)	0.54576 (12)	0.17496 (11)	0.0334 (3)
C16	0.89444 (13)	0.62991 (12)	0.25570 (12)	0.0370 (3)
H16	0.9582	0.6856	0.2784	0.044*
C17	0.77620 (13)	0.63091 (12)	0.30265 (11)	0.0340 (3)
H17	0.7593	0.6875	0.3590	0.041*
F18	1.03312 (8)	0.54292 (8)	0.12881 (8)	0.0482 (2)
C19	0.30688 (12)	0.64839 (12)	0.49708 (10)	0.0312 (3)
H19A	0.2692	0.5866	0.5445	0.037*
H19B	0.3591	0.7012	0.5464	0.037*
O20	0.20865 (9)	0.71516 (8)	0.44560 (8)	0.0363 (2)
C21	0.25020 (16)	0.82639 (13)	0.40291 (12)	0.0446 (4)
H21A	0.2889	0.8737	0.4639	0.067*
H21B	0.1772	0.8694	0.3694	0.067*
H21C	0.3130	0.8125	0.3460	0.067*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0285 (6)	0.0255 (6)	0.0277 (6)	0.0024 (5)	0.0004 (4)	0.0019 (4)
N2	0.0283 (5)	0.0269 (5)	0.0302 (5)	0.0001 (4)	0.0024 (4)	0.0008 (4)
C3	0.0284 (6)	0.0253 (6)	0.0265 (6)	0.0001 (5)	−0.0001 (4)	0.0030 (4)
C4	0.0293 (6)	0.0260 (6)	0.0315 (6)	−0.0014 (5)	0.0017 (5)	0.0010 (5)
N5	0.0294 (5)	0.0259 (5)	0.0291 (5)	0.0012 (4)	0.0026 (4)	−0.0001 (4)
C6	0.0287 (6)	0.0290 (6)	0.0269 (6)	−0.0012 (5)	0.0016 (4)	−0.0001 (5)
C7	0.0311 (7)	0.0337 (7)	0.0394 (7)	0.0012 (5)	0.0013 (5)	−0.0020 (5)
C8	0.0294 (7)	0.0493 (9)	0.0458 (8)	−0.0034 (6)	0.0047 (6)	−0.0048 (6)
C9	0.0398 (8)	0.0453 (8)	0.0424 (8)	−0.0156 (6)	0.0044 (6)	−0.0012 (6)
C10	0.0477 (8)	0.0295 (7)	0.0395 (7)	−0.0060 (6)	0.0000 (6)	0.0004 (5)
C11	0.0328 (7)	0.0294 (6)	0.0346 (6)	0.0004 (5)	0.0008 (5)	−0.0005 (5)
C12	0.0291 (6)	0.0245 (6)	0.0275 (6)	0.0009 (5)	0.0019 (4)	0.0047 (4)
C13	0.0350 (7)	0.0277 (6)	0.0327 (6)	−0.0038 (5)	0.0029 (5)	−0.0005 (5)
C14	0.0398 (7)	0.0288 (6)	0.0345 (6)	0.0000 (5)	0.0095 (5)	−0.0013 (5)
C15	0.0302 (7)	0.0327 (7)	0.0380 (7)	0.0012 (5)	0.0092 (5)	0.0053 (5)
C16	0.0340 (7)	0.0326 (7)	0.0447 (8)	−0.0070 (5)	0.0056 (6)	−0.0033 (6)
C17	0.0351 (7)	0.0295 (6)	0.0377 (7)	−0.0020 (5)	0.0058 (5)	−0.0043 (5)
F18	0.0380 (5)	0.0473 (5)	0.0609 (6)	−0.0051 (4)	0.0216 (4)	−0.0058 (4)
C19	0.0341 (7)	0.0293 (6)	0.0305 (6)	0.0043 (5)	0.0060 (5)	0.0008 (5)
O20	0.0355 (5)	0.0292 (5)	0.0444 (5)	0.0070 (4)	0.0049 (4)	0.0032 (4)
C21	0.0661 (10)	0.0279 (7)	0.0394 (7)	0.0026 (7)	−0.0033 (7)	0.0026 (6)

Geometric parameters (Å, º) top

C1—N2	1.3231 (15)	C11—H11	0.9500
C1—N5	1.3772 (16)	C12—C17	1.3987 (18)
C1—C6	1.4727 (17)	C12—C13	1.4010 (17)
N2—C3	1.3844 (15)	C13—C14	1.3844 (18)
C3—C4	1.3691 (17)	C13—H13	0.9500
C3—C12	1.4666 (17)	C14—C15	1.3738 (19)
C4—N5	1.3725 (16)	C14—H14	0.9500
C4—H4	0.9500	C15—F18	1.3595 (15)
N5—C19	1.4637 (15)	C15—C16	1.3808 (19)
C6—C7	1.3907 (18)	C16—C17	1.3853 (18)
C6—C11	1.4026 (18)	C16—H16	0.9500
C7—C8	1.3882 (19)	C17—H17	0.9500
C7—H7	0.9500	C19—O20	1.4014 (15)
C8—C9	1.388 (2)	C19—H19A	0.9900
C8—H8	0.9500	C19—H19B	0.9900
C9—C10	1.387 (2)	O20—C21	1.4266 (17)
C9—H9	0.9500	C21—H21A	0.9800
C10—C11	1.3846 (19)	C21—H21B	0.9800
C10—H10	0.9500	C21—H21C	0.9800

N2—C1—N5	111.07 (11)	C17—C12—C13	118.20 (12)
N2—C1—C6	123.78 (11)	C17—C12—C3	121.21 (11)
N5—C1—C6	125.09 (11)	C13—C12—C3	120.56 (11)
C1—N2—C3	105.97 (10)	C14—C13—C12	120.95 (12)
C4—C3—N2	109.53 (11)	C14—C13—H13	119.5
C4—C3—C12	128.82 (11)	C12—C13—H13	119.5
N2—C3—C12	121.62 (11)	C15—C14—C13	118.77 (12)
C3—C4—N5	106.71 (11)	C15—C14—H14	120.6
C3—C4—H4	126.6	C13—C14—H14	120.6
N5—C4—H4	126.6	F18—C15—C14	118.59 (12)
C4—N5—C1	106.72 (10)	F18—C15—C16	118.90 (12)
C4—N5—C19	124.72 (11)	C14—C15—C16	122.51 (12)
C1—N5—C19	128.27 (11)	C15—C16—C17	118.19 (12)
C7—C6—C11	118.81 (12)	C15—C16—H16	120.9
C7—C6—C1	123.02 (12)	C17—C16—H16	120.9
C11—C6—C1	118.13 (11)	C16—C17—C12	121.38 (12)
C8—C7—C6	120.16 (13)	C16—C17—H17	119.3
C8—C7—H7	119.9	C12—C17—H17	119.3
C6—C7—H7	119.9	O20—C19—N5	113.27 (10)
C9—C8—C7	120.70 (14)	O20—C19—H19A	108.9
C9—C8—H8	119.7	N5—C19—H19A	108.9
C7—C8—H8	119.7	O20—C19—H19B	108.9
C10—C9—C8	119.54 (13)	N5—C19—H19B	108.9
C10—C9—H9	120.2	H19A—C19—H19B	107.7
C8—C9—H9	120.2	C19—O20—C21	113.37 (11)
C11—C10—C9	120.04 (13)	O20—C21—H21A	109.5
C11—C10—H10	120.0	O20—C21—H21B	109.5
C9—C10—H10	120.0	H21A—C21—H21B	109.5
C10—C11—C6	120.72 (13)	O20—C21—H21C	109.5
C10—C11—H11	119.6	H21A—C21—H21C	109.5
C6—C11—H11	119.6	H21B—C21—H21C	109.5

N5—C1—N2—C3	0.12 (13)	C9—C10—C11—C6	−0.7 (2)
C6—C1—N2—C3	−177.34 (11)	C7—C6—C11—C10	−0.84 (19)
C1—N2—C3—C4	−0.04 (13)	C1—C6—C11—C10	−178.34 (12)
C1—N2—C3—C12	178.28 (10)	C4—C3—C12—C17	13.98 (19)
N2—C3—C4—N5	−0.04 (13)	N2—C3—C12—C17	−163.99 (11)
C12—C3—C4—N5	−178.21 (11)	C4—C3—C12—C13	−168.03 (12)
C3—C4—N5—C1	0.11 (13)	N2—C3—C12—C13	14.00 (17)
C3—C4—N5—C19	174.26 (11)	C17—C12—C13—C14	0.16 (19)
N2—C1—N5—C4	−0.15 (13)	C3—C12—C13—C14	−177.89 (11)
C6—C1—N5—C4	177.27 (11)	C12—C13—C14—C15	−0.4 (2)
N2—C1—N5—C19	−174.02 (11)	C13—C14—C15—F18	−179.97 (12)
C6—C1—N5—C19	3.40 (19)	C13—C14—C15—C16	0.1 (2)
N2—C1—C6—C7	−146.46 (13)	F18—C15—C16—C17	−179.40 (12)
N5—C1—C6—C7	36.44 (18)	C14—C15—C16—C17	0.6 (2)
N2—C1—C6—C11	30.93 (17)	C15—C16—C17—C12	−0.8 (2)
N5—C1—C6—C11	−146.17 (12)	C13—C12—C17—C16	0.49 (19)
C11—C6—C7—C8	1.54 (19)	C3—C12—C17—C16	178.53 (12)
C1—C6—C7—C8	178.91 (12)	C4—N5—C19—O20	99.09 (14)
C6—C7—C8—C9	−0.7 (2)	C1—N5—C19—O20	−88.05 (15)
C7—C8—C9—C10	−0.8 (2)	N5—C19—O20—C21	−76.19 (14)
C8—C9—C10—C11	1.5 (2)

Experimental details

Crystal data
Chemical formula	C₁₇H₁₅FN₂O
M_r	282.31
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	173
a, b, c (Å)	10.524 (1), 11.2480 (11), 11.9810 (12)
β (°)	92.206 (3)
V (Å³)	1417.2 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.40 × 0.30 × 0.10

Data collection
Diffractometer	Bruker SMART CCD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	37183, 3319, 2745
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.655

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.106, 1.07
No. of reflections	3319
No. of parameters	191
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.18

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Acknowledgements

The authors would like to thank the Federal Ministry of Education and Research, Germany, Merckle GmbH, Ulm, Germany, and the Fonds der Chemischen Industrie, Germany, for their generous support of this work.

References

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