Nilutamide

Niraj S Trasi; Phillip E Fanwick; Lynne S Taylor

doi:10.1107/S1600536812003728

. 2012 Feb 4;68(Pt 3):o591. doi: 10.1107/S1600536812003728

Nilutamide

Niraj S Trasi ^a, Phillip E Fanwick ^b, Lynne S Taylor ^a,^*

PMCID: PMC3297316 PMID: 22412506

Abstract

The crystal structure of nilutamide [systematic name: 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione], C₁₂H₁₀F₃N₃O₄, was determined at 150 K. The dihedral angle between the mean planes through the imidazoline [maximum deviation = 0.0396 (14) Å] and benzene rings is 51.49 (5)°. The molecule exhibits intermolecular hydrogen bonding via N—H⋯O interactions, resulting in the formation of chains parallel to the c axis.

Related literature

For the structure of a related compound, see: Cense et al. (1994 ▶).

Experimental

Crystal data

C₁₂H₁₀F₃N₃O₄
M _r = 317.23
Monoclinic,
a = 12.3304 (9) Å
b = 9.8875 (2) Å
c = 12.2118 (3) Å
β = 117.322 (8)°
V = 1322.74 (14) Å³
Z = 4
Cu Kα radiation
μ = 1.31 mm⁻¹
T = 150 K
0.20 × 0.12 × 0.05 mm

Data collection

Rigaku Rapid II diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2001 ▶) T _min = 0.733, T _max = 0.937
13145 measured reflections
2324 independent reflections
2019 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.085
S = 1.12
2324 reflections
206 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.22 e Å⁻³

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 ▶) and a local program based on the method of Prince & Nicholson (1983 ▶); 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 datablock(s) global, I. DOI: 10.1107/S1600536812003728/rz2702sup1.cif

e-68-0o591-sup1.cif^{(24KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812003728/rz2702Isup2.hkl

e-68-0o591-Isup2.hkl^{(114.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812003728/rz2702Isup3.mol

Supplementary material file. DOI: 10.1107/S1600536812003728/rz2702Isup4.cml

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N14—H14⋯O12ⁱ	0.84 (2)	2.06 (2)	2.894 (2)	172.3 (15)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems for financial support (NSF ERCSOPS; EEC-0540855).

supplementary crystallographic information

Comment

The title compound is a potent antiandrogen used primarily in the treatment of advanced stage prostrate cancer. While no single-crystal structure has been reported for this compound before, there have been reported structures for structurally related compounds like flutamide by Cense et al. (1994). However, the molecular arrangement of nilutamide is different from flutamide since flutamide does not exhibit any hydrogen bonding between the NH and the CO.

The imidazoline ring of the title compound (Fig. 1) is roughly planar [maximum deviation 0.0396 (14) Å for atom C15] and forms a dihedral angle of 51.49 (5)° with the benzene ring. The nitro group is tilted by 56.35 (7)° with respect to the benzene ring. In the crystal, molecules are linked by intermolecular N—H···O hydrogen interactions (Table 1) forming chains parallel to the c axis.

Experimental

Nilutamide powder was obtained from Sigma-Aldrich Company and used without further purification.A solution of the compound (20 mg ml^-1) was prepared in acetonitrile in a 3 ml glass vial. The solution was allowed to evaporate slowly by sealing the vial with parafilm and making a few small holes in the parafilm using a fine needle.