2-(Biphenyl-4-yl)acetic acid (felbinac)

Van Eerdenbrugh, B.; Fanwick, P.E.; Taylor, L.S.

doi:10.1107/S1600536810035828

organic compounds

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ISSN: 2056-9890

Volume 66| Part 10| October 2010| Page o2609

doi:10.1107/S1600536810035828

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2-(Biphenyl-4-yl)acetic acid (felbinac)

Bernard Van Eerdenbrugh,^a,^b Phillip E. Fanwick ^c and Lynne S. Taylor ^a ^*

^aDepartment of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA, ^bLaboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium, and ^cDepartment of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA
^*Correspondence e-mail: lstaylor@purdue.edu

(Received 12 August 2010; accepted 6 September 2010; online 25 September 2010)

The structure of the title compound, C₁₄H₁₂O₂, displays the expected intermolecular hydrogen bonding of the carboxylic acid groups, forming dimers. The dihedral angle between the two aromatic rings is 27.01 (7)°.

Related literature

The title compound is a potent non-steroidal anti-inflammatory agent, used to treat muscle inflammation and arthritis. For single-crystal structures of inclusion complexes between felbinac and both heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin and β-cyclodextrin, see: Harata et al. (1992 ) and Wang et al. (2009 ), respectively. For single crystal structures of different complexes of felbinac with tryptamine and 1,2-diphenylethylenediamine (different solvates), see: Koshima et al. (1998 ) and Imai et al. (2007 ), respectively.

Experimental

Crystal data

C₁₄H₁₂O₂
M_r = 212.25
Orthorhombic, P b c n
a = 46.248 (19) Å
b = 6.465 (3) Å
c = 7.470 (3) Å
V = 2233.4 (16) Å³
Z = 8
Cu Kα radiation
μ = 0.64 mm⁻¹
T = 150 K
0.20 × 0.20 × 0.20 mm

Data collection

Rigaku RAPID II diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2001 ) T_min = 0.803, T_max = 0.881
8644 measured reflections
1952 independent reflections
1539 reflections with I > 2σ(I)
R_int = 0.037

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.107
S = 1.08
1952 reflections
150 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1ⁱ	0.98 (2)	1.69 (2)	2.6663 (16)	178 (2)
Symmetry code: (i) $[-x+1, y, -z+{\script{1\over 2}}]$ .

Data collection: CrystalClear (Rigaku, 2001); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEPII (Johnson, 1976 ) and PLATON (Spek, 2009 ); software used to prepare material for publication: SHELXL97 and local programs.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810035828/vm2040sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810035828/vm2040Isup2.hkl

checkCIF report

Comment top

The title compound is a potent non-steroidal anti-inflammatory agent, used to treat muscle inflammation and arthritis. Although the single-crystal structures of inclusion complexes between felbinac and both heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin and β-cyclodextrin have been published (Harata et al., 1992; Wang et al., 2009), that of the pure compound has not been reported. The molecular structure is shown in Figure 1. The expected H-bonded carboxylic acid dimers are formed, with O1···O2 distances of 2.6663 (13) Å. The dihedral angle between the two benzene rings is 27.01 (7)°. Hydrogen bonds between carboxylic acid groups of felbinac are disrupted in the published felbinac-cyclodextrin structures (Harata et al., 1992; Wang et al., 2009). In the inclusion complex between felbinac and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (Harata et al., 1992), no dimers are formed; in that between felbinac and β-cyclodextrin (Wang et al., 2009), face-to-face π-π stackings form the basis for dimer formation. Hydrogen bonds between carboxylic acid groups of felbinac are disrupted in the complexes with tryptamine (Koshima et al., 1998) and 1,2-diphenylethylenediamine (Imai et al., 2007) due to ionic interactions with the amine functions.

Related literature top

The title compound is a potent non-steroidal anti-inflammatory agent, used to

treat muscle inflammation and arthritis. For single-crystal structures of inclusion complexes between felbinac and both heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin and β-cyclodextrin, see: Harata et al. (1992) and Wang et al. (2009), respectively. For single crystal structures of different complexes of felbinac with tryptamine and 1,2-diphenylethylenediamine (different solvates), see: Koshima et al. (1998) and Imai et al. (2007), respectively.

Experimental top

A solution of 2-(biphenyl-4-yl)acetic acid (15 mg ml^-1) was prepared in diethylether. Subsequently, 15 ml of the solution was transferred into a clean crystallization dish (diameter 50 mm; height 35 mm). The vessel was partially covered with a plastic sheet and the solution was allowed to slowly evaporate overnight.

Computing details top

Data collection: CrystalClear (Rigaku, 2001); cell refinement: CrystalClear (Rigaku, 2001); data reduction: CrystalClear (Rigaku, 2001); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELX97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local programs.

Figures top

Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atomic numbering. H atoms are presented as small spheres of arbitrary radius.

2-(Biphenyl-4-yl)acetic acid top

Crystal data top

C₁₄H₁₂O₂	F(000) = 896
M_r = 212.25	D_x = 1.262 Mg m⁻³
Orthorhombic, Pbcn	Cu - Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2n 2ab	Cell parameters from 8644 reflections
a = 46.248 (19) Å	θ = 6–66°
b = 6.465 (3) Å	µ = 0.64 mm⁻¹
c = 7.470 (3) Å	T = 150 K
V = 2233.4 (16) Å³	Chunk, colourless
Z = 8	0.20 × 0.20 × 0.20 mm

Data collection top

Rigaku RAPID II diffractometer	1539 reflections with I > 2σ(I)
Confocal optics monochromator	R_int = 0.037
ω scans	θ_max = 66.5°, θ_min = 6.6°
Absorption correction: multi-scan (CrystalClear; Rigaku, 2001)	h = −53→54
T_min = 0.803, T_max = 0.881	k = −7→7
8644 measured reflections	l = −8→8
1952 independent reflections

Refinement top

Refinement on F²	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0586P)² + 0.0731P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.038	(Δ/σ)_max = 0.001
wR(F²) = 0.107	Δρ_max = 0.21 e Å⁻³
S = 1.08	Δρ_min = −0.12 e Å⁻³
1952 reflections	Extinction correction: SHELXL97 (Sheldrick, 2008)
150 parameters	Extinction coefficient: 0.92E-02
0 restraints

Crystal data top

C₁₄H₁₂O₂	V = 2233.4 (16) Å³
M_r = 212.25	Z = 8
Orthorhombic, Pbcn	Cu - Kα radiation
a = 46.248 (19) Å	µ = 0.64 mm⁻¹
b = 6.465 (3) Å	T = 150 K
c = 7.470 (3) Å	0.20 × 0.20 × 0.20 mm

Data collection top

Rigaku RAPID II diffractometer	1952 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2001)	1539 reflections with I > 2σ(I)
T_min = 0.803, T_max = 0.881	R_int = 0.037
8644 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	0 restraints
wR(F²) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	Δρ_max = 0.21 e Å⁻³
1952 reflections	Δρ_min = −0.12 e Å⁻³
150 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. Outlier data were removed using a local program based on the method of Prince and Nicholson.

Refinement on F² for ALL reflections except for 0 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating R_factor_obs 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
O1	0.465961 (19)	0.26139 (14)	0.29970 (13)	0.0659 (3)
O2	0.50183 (2)	0.25189 (14)	0.49623 (15)	0.0673 (3)
C11	0.36381 (3)	0.24813 (16)	0.46896 (16)	0.0459 (3)
C12	0.38092 (3)	0.07334 (19)	0.44073 (17)	0.0537 (3)
C13	0.40981 (3)	0.0723 (2)	0.48829 (18)	0.0580 (4)
C14	0.42282 (3)	0.24426 (18)	0.56461 (17)	0.0519 (4)
C15	0.40583 (3)	0.4174 (2)	0.59492 (18)	0.0571 (4)
C16	0.37693 (3)	0.41946 (19)	0.54734 (17)	0.0549 (4)
C17	0.45452 (3)	0.24152 (19)	0.61233 (19)	0.0606 (4)
C18	0.47426 (3)	0.25310 (17)	0.45355 (19)	0.0513 (4)
C21	0.33265 (3)	0.25021 (16)	0.41626 (16)	0.0462 (3)
C22	0.31270 (2)	0.37583 (18)	0.50399 (17)	0.0543 (4)
C23	0.28391 (3)	0.3774 (2)	0.45408 (18)	0.0591 (4)
C24	0.27427 (3)	0.25357 (19)	0.3176 (2)	0.0594 (4)
C25	0.29358 (3)	0.1274 (2)	0.2301 (2)	0.0628 (4)
C26	0.32239 (3)	0.1263 (2)	0.27863 (18)	0.0566 (4)
H2	0.5133 (4)	0.258 (2)	0.386 (3)	0.105 (7)*
H12	0.3726	−0.0465	0.3881	0.064*
H13	0.4210	−0.0489	0.4683	0.070*
H15	0.4141	0.5363	0.6491	0.069*
H16	0.3658	0.5404	0.5686	0.066*
H22	0.3190	0.4617	0.5996	0.065*
H23	0.2707	0.4652	0.5149	0.071*
H24	0.2545	0.2549	0.2839	0.071*
H25	0.2871	0.0405	0.1357	0.075*
H26	0.3355	0.0388	0.2164	0.068*
H17A	0.4587	0.3598	0.6925	0.073*
H17B	0.4588	0.1130	0.6794	0.073*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0465 (6)	0.0959 (8)	0.0552 (6)	−0.0007 (4)	−0.0058 (4)	0.0046 (5)
O2	0.0459 (6)	0.0945 (9)	0.0617 (6)	0.0005 (4)	−0.0098 (5)	−0.0014 (5)
C11	0.0472 (7)	0.0521 (8)	0.0384 (7)	−0.0008 (5)	0.0040 (5)	−0.0001 (5)
C12	0.0536 (8)	0.0521 (7)	0.0555 (8)	−0.0006 (6)	0.0023 (6)	−0.0078 (6)
C13	0.0545 (8)	0.0584 (8)	0.0611 (9)	0.0074 (6)	0.0030 (6)	−0.0049 (7)
C14	0.0499 (8)	0.0642 (9)	0.0416 (7)	−0.0003 (5)	0.0006 (5)	0.0029 (6)
C15	0.0571 (8)	0.0584 (8)	0.0559 (8)	−0.0041 (6)	−0.0027 (6)	−0.0090 (7)
C16	0.0529 (8)	0.0530 (7)	0.0587 (8)	0.0032 (6)	−0.0010 (6)	−0.0090 (6)
C17	0.0550 (9)	0.0761 (10)	0.0508 (8)	0.0019 (6)	−0.0054 (6)	−0.0001 (7)
C18	0.0469 (7)	0.0527 (8)	0.0543 (8)	0.0006 (5)	−0.0104 (6)	−0.0015 (6)
C21	0.0485 (8)	0.0490 (7)	0.0411 (7)	−0.0024 (5)	0.0041 (5)	0.0017 (5)
C22	0.0539 (8)	0.0611 (9)	0.0479 (7)	0.0028 (6)	0.0003 (6)	−0.0072 (6)
C23	0.0518 (8)	0.0678 (9)	0.0576 (9)	0.0068 (6)	0.0047 (6)	−0.0003 (7)
C24	0.0487 (8)	0.0666 (9)	0.0628 (9)	−0.0047 (6)	−0.0040 (6)	0.0066 (7)
C25	0.0585 (9)	0.0688 (10)	0.0612 (9)	−0.0073 (6)	−0.0072 (6)	−0.0109 (7)
C26	0.0551 (8)	0.0603 (9)	0.0544 (8)	−0.0010 (6)	0.0025 (6)	−0.0103 (6)

Geometric parameters (Å, º) top

O1—C18	1.2128 (17)	C17—C18	1.499 (2)
O2—C18	1.3144 (15)	C17—H17A	0.9900
O2—H2	0.98 (2)	C17—H17B	0.9900
C11—C16	1.3921 (16)	C21—C26	1.3869 (17)
C11—C12	1.3957 (16)	C21—C22	1.3930 (16)
C11—C21	1.4937 (18)	C22—C23	1.3827 (16)
C12—C13	1.3822 (16)	C22—H22	0.9500
C12—H12	0.9500	C23—C24	1.3710 (18)
C13—C14	1.3870 (17)	C23—H23	0.9500
C13—H13	0.9500	C24—C25	1.3749 (18)
C14—C15	1.3865 (16)	C24—H24	0.9500
C14—C17	1.5088 (18)	C25—C26	1.3811 (16)
C15—C16	1.3830 (16)	C25—H25	0.9500
C15—H15	0.9500	C26—H26	0.9500
C16—H16	0.9500

C18—O2—H2	108.7 (11)	C14—C17—H17B	108.80
C16—C11—C12	117.42 (12)	H17A—C17—H17B	107.70
C16—C11—C21	121.62 (10)	O1—C18—O2	122.48 (13)
C12—C11—C21	120.97 (11)	O1—C18—C17	124.01 (12)
C13—C12—C11	120.89 (12)	O2—C18—C17	113.50 (13)
C13—C12—H12	119.60	C26—C21—C22	117.31 (12)
C11—C12—H12	119.60	C26—C21—C11	121.35 (10)
C12—C13—C14	121.41 (11)	C22—C21—C11	121.34 (11)
C12—C13—H13	119.30	C23—C22—C21	121.02 (12)
C14—C13—H13	119.30	C23—C22—H22	119.50
C15—C14—C13	117.92 (12)	C21—C22—H22	119.50
C15—C14—C17	121.45 (11)	C24—C23—C22	120.62 (12)
C13—C14—C17	120.63 (11)	C24—C23—H23	119.70
C16—C15—C14	120.90 (12)	C22—C23—H23	119.70
C16—C15—H15	119.50	C23—C24—C25	119.27 (13)
C14—C15—H15	119.50	C23—C24—H24	120.40
C15—C16—C11	121.46 (11)	C25—C24—H24	120.40
C15—C16—H16	119.30	C24—C25—C26	120.31 (13)
C11—C16—H16	119.30	C24—C25—H25	119.80
C18—C17—C14	113.85 (12)	C26—C25—H25	119.80
C18—C17—H17A	108.80	C25—C26—C21	121.47 (12)
C14—C17—H17A	108.80	C25—C26—H26	119.30
C18—C17—H17B	108.80	C21—C26—H26	119.30

C16—C11—C12—C13	−0.35 (19)	C14—C17—C18—O2	179.61 (9)
C21—C11—C12—C13	179.48 (11)	C16—C11—C21—C26	152.94 (12)
C11—C12—C13—C14	−0.3 (2)	C12—C11—C21—C26	−26.89 (17)
C12—C13—C14—C15	1.1 (2)	C16—C11—C21—C22	−27.41 (17)
C12—C13—C14—C17	−178.81 (12)	C12—C11—C21—C22	152.77 (12)
C13—C14—C15—C16	−1.2 (2)	C26—C21—C22—C23	−0.55 (17)
C17—C14—C15—C16	178.71 (12)	C11—C21—C22—C23	179.79 (11)
C14—C15—C16—C11	0.5 (2)	C21—C22—C23—C24	0.58 (19)
C12—C11—C16—C15	0.25 (19)	C22—C23—C24—C25	−0.14 (19)
C21—C11—C16—C15	−179.59 (11)	C23—C24—C25—C26	−0.3 (2)
C15—C14—C17—C18	−106.63 (14)	C24—C25—C26—C21	0.3 (2)
C13—C14—C17—C18	73.25 (15)	C22—C21—C26—C25	0.09 (18)
C14—C17—C18—O1	−0.88 (18)	C11—C21—C26—C25	179.76 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1ⁱ	0.98 (2)	1.69 (2)	2.6663 (16)	178 (2)

Symmetry code: (i) −x+1, y, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₂O₂
M_r	212.25
Crystal system, space group	Orthorhombic, Pbcn
Temperature (K)	150
a, b, c (Å)	46.248 (19), 6.465 (3), 7.470 (3)
V (Å³)	2233.4 (16)
Z	8
Radiation type	Cu - Kα
µ (mm⁻¹)	0.64
Crystal size (mm)	0.20 × 0.20 × 0.20

Data collection
Diffractometer	Rigaku RAPID II diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2001)
T_min, T_max	0.803, 0.881
No. of measured, independent and observed [I > 2σ(I)] reflections	8644, 1952, 1539
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.107, 1.08
No. of reflections	1952
No. of parameters	150
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.12

Computer programs: CrystalClear (Rigaku, 2001), SIR2004 (Burla et al., 2005), SHELX97 (Sheldrick, 2008), ORTEPII (Johnson, 1976) and PLATON (Spek, 2009), SHELXL97 (Sheldrick, 2008) and local programs.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1ⁱ	0.98 (2)	1.69 (2)	2.6663 (16)	178 (2)

Symmetry code: (i) −x+1, y, −z+1/2.

Acknowledgements

The authors would like to thank the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems for financial support (NSF ERC-SOPS; EEC-0540855). The authors thank the National Science Foundation, Directorate for Mathematical & Physical Sciences, Division of Materials Research for financial support (NSF MPS-DMR; DMR-0804609). BVE is a Postdoctoral Researcher of the `Fonds voor Wetenschappelijk Onderzoek', Flanders, Belgium.

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