1-[(Biphenyl-4-yl)(phen­yl)meth­yl]-1H-imidazole (bifonazole)

Bernard Van Eerdenbrugh; Phillip E Fanwick; Lynne S Taylor

doi:10.1107/S1600536810037876

. 2010 Sep 30;66(Pt 10):o2649. doi: 10.1107/S1600536810037876

1-[(Biphenyl-4-yl)(phenyl)methyl]-1H-imidazole (bifonazole)

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

PMCID: PMC2983152 PMID: 21587620

Abstract

In the title compound, C₂₂H₁₈N₂, the dihedral angles formed by the imidazole ring with the phenyl ring and the benzene ring of the biphenyl group are 87.02 (5) and 78.20 (4)°, respectively. In the crystal, molecules interact through intermolecular C—H⋯N hydrogen bonds, forming chains parallel to the b axis. These chains are further linked into a three-dimensional network by C—H⋯π stacking interactions

Related literature

For a review of the antimicrobial activity of bifonazole and its therapeutic use in superficial mycoses, see: Lackner and Clissold (1989 ▶).

Experimental

Crystal data

C₂₂H₁₈N₂
M _r = 310.40
Monoclinic,
a = 7.9737 (7) Å
b = 6.2591 (6) Å
c = 33.265 (3) Å
β = 93.805 (8)°
V = 1656.5 (3) Å³
Z = 4
Cu Kα radiation
μ = 0.56 mm⁻¹
T = 150 K
0.20 × 0.20 × 0.04 mm

Data collection

Rigaku RAPID II diffractometer
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.860, T _max = 0.979
19391 measured reflections
3064 independent reflections
2801 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.107
S = 1.06
3064 reflections
218 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrystalClear (Rigaku, 2001 ▶); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; 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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810037876/rz2487sup1.cif

e-66-o2649-sup1.cif^{(20.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810037876/rz2487Isup2.hkl

e-66-o2649-Isup2.hkl^{(150.4KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg1, Cg2 and Cg3 are the centroids of the N1/N2/C20–C22, C1–C6 and C14–C19 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯N2ⁱ	1.00	2.45	3.418 (2)	161
C3—H3⋯Cg1ⁱⁱ	0.95	2.76	3.609 (2)	149
C6—H6⋯Cg1ⁱⁱⁱ	0.95	2.96	3.900 (3)	171
C18—H18⋯Cg2^iv	0.95	3.01	3.797 (7)	141
C21—H21⋯Cg2^v	0.95	2.76	3.694 (7)	170
C12—H12⋯Cg3^vi	0.95	2.87	3.737 (5)	153

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) .

Acknowledgments

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.

supplementary crystallographic information

Comment

Bifonazole is a broad-spectrum antifungal agent, mainly used by topical application in the treatment of fungal skin infections, including nail infections (Lackner & Clissold, 1989). In the crystal structure of the racemate, layers of the R and S enantiomer alternate along the c axis. Figure 1 shows the S configuration of the chiral center at atom C7. The dihedral angles between the different rings are 26.17 (8)° for the two aromatic rings of the biphenyl group, 101.80 (4)° for the imidazole ring and the benzene ring of the biphenyl group, 62.34 (5)° for the phenyl ring and the benzene ring of the biphenyl group, and 92.98 (5)° for the imidazole ring and the phenyl ring. In the crystal structure, molecules are linked by intermolecular C—H···N hydrogen bonds (Table 1) into chains running parallel to the b axis. The chains are further connected by C—H···π stacking interactions to form a three-dimensional network.

Experimental

A saturated solution of the title compound was prepared by adding an excess of powder to 20 ml of diethyl ether. Subsequent to stirring the suspension overnight, filtration was performed using a 0.2 µm PTFE syringe filter (13 mm, VWR International, LLC, West Chester, PA, USA). The solution was transferred into a 20 ml scintillation vial in 20 ml scintillation vials (Research Products International Corp., Mt. Prospect, IL, USA) and three holes were pierced in the cap of the vial to allow the solvent to slowly evaporate. After one week, all solvent had evaporated and crystals of the title compound were obtained.