Crystal structure of (2-{[3,5-bis­(1,1-di­methyl­eth­yl)-4-hy­droxy­phen­yl](5-methyl-2H-pyrrol-2-yl­idene)meth­yl}-5-methyl-1H-pyrrolido-κ2 N,N′)di­fluoridoboron

Yukio Morimoto; Keizo Ogawa; Yoshihiro Uto; Hideko Nagasawa; Hitoshi Hori

doi:10.1107/S2056989015015789

. 2015 Aug 29;71(Pt 9):o694–o695. doi: 10.1107/S2056989015015789

Crystal structure of (2-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl](5-methyl-2H-pyrrol-2-ylidene)methyl}-5-methyl-1H-pyrrolido-κ² N,N′)difluoridoboron

Yukio Morimoto ^a,^*, Keizo Ogawa ^b, Yoshihiro Uto ^c, Hideko Nagasawa ^d, Hitoshi Hori ^e

PMCID: PMC4555381 PMID: 26396909

Abstract

The title compound, C₂₅H₃₁BF₂N₂O, is a potential boron tracedrug in boron neutron capture therapy (BNCT), in which the B atom adopts a distorted BN₂F₂ tetrahedral geometry: it is soluble in dimethyl sulfoxide, dimethylformamide and methanol. The pyrrolylidenemethylpyrrole triple fused ring system is almost planar (r.m.s. deviation = 0.031 Å) and subtends a dihedral angle of 47.09 (5)° with the plane of the pendant phenol ring. The phenol –OH group is blocked from forming hydrogen bonds by the adjacent bulky tert-butyl groups. In the crystal, inversion dimers linked by pairs of very weak C—H⋯F interactions generate R ₂ ²(22) loops.

Keywords: crystal structure, boron tracedrug, boron neutron capture therapy (BNCT)

Related literature

For background to tracer compounds for BNCT, see: Hori et al. (2010 ▸, 2012 ▸). For further synthetic details, see: Nakata et al. (2011 ▸). graphic file with name e-71-0o694-scheme1.jpg

Experimental

Crystal data

C₂₅H₃₁BF₂N₂O
M _r = 424.34
Triclinic,
a = 9.2518 (2) Å
b = 10.0975 (2) Å
c = 12.5142 (3) Å
α = 79.364 (6)°
β = 89.613 (6)°
γ = 83.367 (6)°
V = 1141.18 (5) Å³
Z = 2
Cu Kα radiation
μ = 0.69 mm⁻¹
T = 296 K
0.16 × 0.08 × 0.04 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
Absorption correction: multi-scan (ABSCOR; Rigaku, 1995 ▸) T _min = 0.749, T _max = 0.973
13606 measured reflections
4044 independent reflections
3644 reflections with F ² > 2.0σ(F ²)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.115
S = 1.09
4044 reflections
289 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: RAPID-AUTO (Rigaku, 2011 ▸); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: Il Milione (Burla et al., 2007 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: CrystalStructure (Rigaku, 2011 ▸); software used to prepare material for publication: CrystalStructure.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015015789/hb7487sup1.cif

e-71-0o694-sup1.cif^{(24.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015015789/hb7487Isup2.hkl

e-71-0o694-Isup2.hkl^{(198.2KB, hkl)}

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015015789/hb7487fig1.tif

Molecular structure of the compound. Displacement ellipsoids are shown at the 50% probability level. H atoms are depicted as small spheres of arbitrary radius.

CCDC reference: 1420063

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C12H12CF2ⁱ	0.96	2.54	3.4464(18)	158

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Dr Akihito Yamano (Rigaku Co. Ltd) for his kind technical support of data collection, and YM is grateful to the Grant-in-Aid for the project of a molecular mechanism of emotional control (Customer Care Plan 2014, 2015).

supplementary crystallographic information

S1. Chemical context

\ For the synthesis of 2-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl](5-methyl-2H-pyrrol-2-\ ylidene)methyl}-5-methyl-1H-pyrrolido-κ²N,N']\ difluoridoboron see: Nakata, et al. (2011). The compound: CAS Registry Number 1415304-92-5. The ring compound binding BF₂ is a contracted form given in IUPAC.

S2. Structural commentary

The traceability of boron tracedrugs is based on the neutron capture activity of the stable isotope boron-10 embedded in the drug. Thus, newly designed boron tracedrugs would be novel pharmaceuticals, the structures of which would always include natural boron (B¹¹, 80.4%; B¹⁰, 19.6%), as tracers, embedded deeply in their skeletons or scaffolds. The compound is used at a cancer therapy by an irradiation of neutron, since B¹⁰ atom generates a high energy alpha-line within a cancer cell by fission of the atom. The compound is required to keep a suitable three-dimensional structure until reaching cancer cell via intravenous injection and an irradiation of neutron. Our group has developed boron tracedrugs in use of boron-neutron reaction (Hori, et al. 2010, 2012), in this study a suitable compound has been reported and presents that two bulky rings tilt each other to avoid steric hindrance.

S3. Synthesis and crystallization

Crystals were obtained from methanol solvent at room temperature by slow evaporation. Crystal structure has no present of solvent molecule. The synthesis of the title compound was decribed by Nakata et al. (2011). The compound: CAS Registry Number 1415304-92-5. The ring compound binding BF₂ is a contracted form given in IUPAC.

S4. Refinement

All hydrogen atoms were placed in the calculated positions and constrained their parent atoms with a C—H distances of 0.95 Å (aromatic) and 0.99 Å (methylene) and with Uiso(H) = 1.2Ueq(C), and 0.98 Å for CH3 [Uiso(H)= 1.5Ueq(C)].