Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Previous article
Next article
Previous article
Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Next article

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 12| December 2011| Pages o3313-o3314
https://doi.org/10.1107/S1600536811047738

Benzyl 2-{[2,8-bis­­(tri­fluoro­meth­yl)quinolin-4-yl](hy­dr­oxy)meth­yl}piperidine-1-carboxyl­ate

Marcus V. N. de Souza,a Raoni S. B. Gonçalves,a James L. Wardell,b‡ Solange M. S. V. Wardellc and Edward R. T. Tiekinkd*

aFundaçaõ Oswaldo Cruz, Instituto de Tecnologia, em Fármacos–Farmanguinhos, R. Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil, bCentro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz (FIOCRUZ), Casa Amarela, Campus de Manguinhos, Av. Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil, cCHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland, and dDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
*Correspondence e-mail: edward.tiekink@gmail.com

(Received 9 November 2011; accepted 10 November 2011; online 16 November 2011)

The title mol­ecule, C25H22F6N2O3, adopts an open conformation whereby the quinoline and carboxyl­ate ester groups are orientated in opposite directions but to the same side of the piperidine ring so that the mol­ecule has an approximate U-shape. The piperidine ring adopts a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R22(14) loops.

Related literature

For background to the anti-mycobacterial activity of mefloquine, see: Gonçalves et al. (2010[Gonçalves, R. S. B., Kaiser, C. R., Lourenço, M. C. S., de Souza, M. V. N., Wardell, J. L., Wardell, S. M. S. V. & da Silva, A. D. (2010). Eur. J. Med. Chem. 45, 6095-6100.]); Mao et al. (2007[Mao, J., Wang, Y., Wan, B., Kozikowski, A. P. S. G. & Franzblau, S. G. (2007). ChemMedChem, 2, 1624-1630.]); Maguire et al. (2006[Maguire, J. D., Krisin, Marwoto, H., Richie, T. L., Fryauff, D. J. & Baird, J. K. (2006). Clin. Infect. Dis. 42, 1067-1072.]). For the synthesis, see: Grellepois et al. (2005[Grellepois, F., Grellier, P., Bonnet-Delpon, D. & Bégué, J. P. (2005). ChemBioChem, 6, 648-652.]). For related structures, see: Gonçalves et al. (2011a[Gonçalves, R. S. B., Souza, M. V. N. de, Wardell, J. L., Wardell, S. M. S. V. & Tiekink, E. R. T. (2011a). Acta Cryst. E67, o3315-o3316.],b[Gonçalves, R. S. B., Kaiser, C. R., Souza, M. V. N. de, Wardell, J. L., Wardell, S. M. S. V. & Tiekink, E. R. T. (2011b). Acta Cryst. E67, o1656-o1657.]); Wardell et al. (2010[Wardell, J. L., Wardell, S. M. S. V., Tiekink, E. R. T. & Lima, G. M. de (2010). Acta Cryst. E66, m336-m337.], 2011a[Wardell, J. L., de Souza, M. V. N., Wardell, S. M. S. V. & Lourenço, M. C. S. (2011a). J. Mol. Struct. 990, 67-74.],b[Wardell, S. M. S. V., Wardell, J. L., Skakle, J. M. S. & Tiekink, E. R. T. (2011b). Z. Kristallogr. 226, 68-77.]); Pitaluga et al. (2010[Pitaluga, A. Jr, Prado, L. D., Seiceira, R., Wardell, J. L. & Wardell, S. M. S. V. (2010). Int. J. Pharm. 398, 50-60.]). For ring conformations, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]).

[Scheme 1]

Experimental

Crystal data

  • C25H22F6N2O3

  • Mr = 512.45

  • Monoclinic, P 21 /n

  • a = 12.7793 (5) Å

  • b = 13.9970 (7) Å

  • c = 13.2188 (9) Å

  • β = 109.999 (8)°

  • V = 2221.9 (2) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.13 mm−1

  • T = 100 K

  • 0.15 × 0.11 × 0.04 mm
Data collection

  • Rigaku Saturn724+ diffractometer

  • Absorption correction: multi-scan (CrystalClear-SM Expert; Rigaku, 2011[Rigaku (2011). CrystalClear-SM Expert. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.757, Tmax = 1.000

  • 10271 measured reflections

  • 5060 independent reflections

  • 4132 reflections with I > 2σ(I)

  • Rint = 0.026
Refinement

  • R[F2 > 2σ(F2)] = 0.039

  • wR(F2) = 0.107

  • S = 1.00

  • 5060 reflections

  • 328 parameters

  • 1 restraint

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.34 e Å−3

  • Δρmin = −0.32 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O1—H1o⋯O3i 0.84 (1) 1.90 (1) 2.7294 (14) 172 (2)
Symmetry code: (i) -x+1, -y+1, -z+2.

Data collection: CrystalClear-SM Expert (Rigaku, 2011[Rigaku (2011). CrystalClear-SM Expert. Rigaku Corporation, Tokyo, Japan.]); cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]) and DIAMOND (Brandenburg, 2006[Brandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536811047738/hb6498sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811047738/hb6498Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811047738/hb6498Isup3.cml

checkCIF report


Comment top

For some decades, in combination with other drugs, mefloquine has been used in the prevention and treatment of malaria (Maguire et al., 2006). The activity of mefloquine has been investigated against other diseases more recently, for example, as anti-viral and anti-tubercular agents (Mao et al., 2007). In continuation of on-going structural and biological studies on mefloquine derivatives (Gonçalves et al., 2010, 2011a, 2011b; Wardell, et al., 2010; 2011a; 2011b; Pitaluga et al., 2010), we now report the crystal and molecular structure of the title compound, (I).

In the molecule of (I), Fig. 1, the hydroxyl group lies to one side of the plane through the quinolinyl residue and the substituted piperidine ring to other with the carboxylate ester directed away from the rest of the molecule. The residues lie to the same side of the piperidine ring so that the molecule has a U-shape. The piperidine ring has a distorted boat conformation with ring puckering parameters: q2 = 0.7644 (16) Å; q3 = -0.0283 (16) Å; QT = 0.7649 (16) Å; and θ = 92.12 (12) ° (Cremer & Pople, 1975). Mefloquine used as a reagent was a racemate. The sum of the angles at the trisubstituted N2 is 356° indicating a very near planar geometry, and hence an achiral centre. The configurations of the C12 and C13 in the illustrated molecule, Fig. 1, are R, S and R, respectively. The crystal structure contains an equal amount of the opposite enantiomer.

The most prominent intermolecular interactions in the crystal structure are O—H···O hydrogen bonds that lead to the formation of centrosymmetric dimeric aggregates via 14-membered {···HOC2NCO}2 synthons, Fig. 1 and Table 1.

Related literature top

For background to the anti-mycobacterial activity of mefloquine, see: Gonçalves et al. (2010); Mao et al. (2007); Maguire et al. (2006). For the synthesis, see: Grellepois et al. (2005). For related structures, see: Gonçalves et al. (2011a,b); Wardell et al. (2010, 2011a,b); Pitaluga et al. (2010). For ring conformations, see: Cremer & Pople (1975).

Experimental top

Benzyl 2-[[2,8-bis(trifluoromethyl)-4-quinolinyl](hydroxy)methyl]tetrahydro-1(2H)-pyridine carboxylate was prepared similarly to tert-butyl 2-[[2,8-bis(trifluoromethyl)-4-quinolinyl](hydroxy)methyl]tetrahydro-1(2H)-pyridine carboxylate, following a published procedure (Grellepois et al., 2005), from benzyl chloroformate and mefloquine in the presence of Et3N. Colourless plates of (I) were grown from an EtOH solution; M.pt. 445–447 K. MS 535.3 [M + Na].

Refinement top

The C-bound H atoms were geometrically placed (C—H = 0.95–1.00 Å) and refined as riding with Uiso(H) = 1.2Ueq(C). The O—H H atom was located in a difference map and refined with O—H = 0.84±0.01 Å with Uiso(H) = 1.5Ueq(O).

Structure description top

For some decades, in combination with other drugs, mefloquine has been used in the prevention and treatment of malaria (Maguire et al., 2006). The activity of mefloquine has been investigated against other diseases more recently, for example, as anti-viral and anti-tubercular agents (Mao et al., 2007). In continuation of on-going structural and biological studies on mefloquine derivatives (Gonçalves et al., 2010, 2011a, 2011b; Wardell, et al., 2010; 2011a; 2011b; Pitaluga et al., 2010), we now report the crystal and molecular structure of the title compound, (I).

In the molecule of (I), Fig. 1, the hydroxyl group lies to one side of the plane through the quinolinyl residue and the substituted piperidine ring to other with the carboxylate ester directed away from the rest of the molecule. The residues lie to the same side of the piperidine ring so that the molecule has a U-shape. The piperidine ring has a distorted boat conformation with ring puckering parameters: q2 = 0.7644 (16) Å; q3 = -0.0283 (16) Å; QT = 0.7649 (16) Å; and θ = 92.12 (12) ° (Cremer & Pople, 1975). Mefloquine used as a reagent was a racemate. The sum of the angles at the trisubstituted N2 is 356° indicating a very near planar geometry, and hence an achiral centre. The configurations of the C12 and C13 in the illustrated molecule, Fig. 1, are R, S and R, respectively. The crystal structure contains an equal amount of the opposite enantiomer.

The most prominent intermolecular interactions in the crystal structure are O—H···O hydrogen bonds that lead to the formation of centrosymmetric dimeric aggregates via 14-membered {···HOC2NCO}2 synthons, Fig. 1 and Table 1.

For background to the anti-mycobacterial activity of mefloquine, see: Gonçalves et al. (2010); Mao et al. (2007); Maguire et al. (2006). For the synthesis, see: Grellepois et al. (2005). For related structures, see: Gonçalves et al. (2011a,b); Wardell et al. (2010, 2011a,b); Pitaluga et al. (2010). For ring conformations, see: Cremer & Pople (1975).

Computing details top

Data collection: CrystalClear-SM Expert (Rigaku, 2011); cell refinement: CrystalClear-SM Expert (Rigaku, 2011); data reduction: CrystalClear-SM Expert (Rigaku, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.
[Figure 2] Fig. 2. Centrosymmetric aggregate mediated by O—H···O hydrogen bonds (orange dashed lines) in the crystal structure of (I).
Benzyl 2-{[2,8-bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidine-1- carboxylate top
Crystal data top
C25H22F6N2O3F(000) = 1056
Mr = 512.45Dx = 1.532 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 8584 reflections
a = 12.7793 (5) Åθ = 3.1–27.5°
b = 13.9970 (7) ŵ = 0.13 mm−1
c = 13.2188 (9) ÅT = 100 K
β = 109.999 (8)°Plate, colourless
V = 2221.9 (2) Å30.15 × 0.11 × 0.04 mm
Z = 4
Data collection top
Rigaku Saturn724+
diffractometer		5060 independent reflections
Radiation source: Rotating Anode4132 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.026
Detector resolution: 28.5714 pixels mm-1θmax = 27.5°, θmin = 3.1°
profile data from ω–scansh = −15→16
Absorption correction: multi-scan
(CrystalClear-SM Expert; Rigaku, 2011)		k = −15→18
Tmin = 0.757, Tmax = 1.000l = −14→17
10271 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.039Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.107H atoms treated by a mixture of independent and constrained refinement
S = 1.00 w = 1/[σ2(Fo2) + (0.0549P)2 + 0.9076P]
where P = (Fo2 + 2Fc2)/3
5060 reflections(Δ/σ)max < 0.001
328 parametersΔρmax = 0.34 e Å−3
1 restraintΔρmin = −0.32 e Å−3
Crystal data top
C25H22F6N2O3V = 2221.9 (2) Å3
Mr = 512.45Z = 4
Monoclinic, P21/nMo Kα radiation
a = 12.7793 (5) ŵ = 0.13 mm−1
b = 13.9970 (7) ÅT = 100 K
c = 13.2188 (9) Å0.15 × 0.11 × 0.04 mm
β = 109.999 (8)°
Data collection top
Rigaku Saturn724+
diffractometer		5060 independent reflections
Absorption correction: multi-scan
(CrystalClear-SM Expert; Rigaku, 2011)		4132 reflections with I > 2σ(I)
Tmin = 0.757, Tmax = 1.000Rint = 0.026
10271 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0391 restraint
wR(F2) = 0.107H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.34 e Å−3
5060 reflectionsΔρmin = −0.32 e Å−3
328 parameters
Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
xyzUiso*/Ueq
F10.06301 (8)0.63866 (8)0.42728 (8)0.0347 (3)
F20.08200 (10)0.59309 (10)0.27995 (8)0.0472 (3)
F30.00983 (8)0.49890 (9)0.36550 (11)0.0490 (3)
F40.24269 (7)0.32103 (7)0.22775 (7)0.0244 (2)
F50.40411 (8)0.31616 (7)0.21097 (7)0.0268 (2)
F60.32339 (7)0.45128 (7)0.20711 (7)0.0223 (2)
O10.34838 (8)0.58357 (7)0.75929 (8)0.0177 (2)
H1o0.3897 (13)0.6035 (13)0.8197 (10)0.026*
O20.54803 (8)0.32514 (8)0.88013 (8)0.0172 (2)
O30.53313 (8)0.33958 (7)1.04525 (8)0.0167 (2)
N10.24628 (9)0.47056 (9)0.38278 (9)0.0148 (2)
N20.40608 (9)0.40943 (8)0.89798 (9)0.0132 (2)
C10.20188 (11)0.52274 (10)0.44060 (11)0.0157 (3)
C20.24724 (11)0.53657 (10)0.55218 (11)0.0153 (3)
H20.21150.57730.58790.018*
C30.34448 (11)0.49011 (10)0.60906 (11)0.0135 (3)
C40.39716 (11)0.43306 (10)0.55111 (11)0.0131 (3)
C50.49874 (11)0.38293 (10)0.60028 (11)0.0156 (3)
H50.53360.38480.67630.019*
C60.54664 (12)0.33218 (11)0.53960 (12)0.0184 (3)
H60.61490.29970.57370.022*
C70.49589 (12)0.32732 (10)0.42648 (12)0.0178 (3)
H70.53050.29200.38520.021*
C80.39727 (11)0.37307 (10)0.37610 (11)0.0148 (3)
C90.34484 (11)0.42711 (10)0.43713 (11)0.0132 (3)
C100.08955 (13)0.56455 (12)0.37809 (12)0.0234 (3)
C110.34203 (12)0.36577 (11)0.25637 (12)0.0188 (3)
C120.38962 (11)0.49779 (10)0.73029 (11)0.0136 (3)
H120.47280.50040.75530.016*
C130.35295 (11)0.40908 (10)0.77995 (11)0.0130 (3)
H130.37850.35070.75150.016*
C140.33521 (11)0.43906 (11)0.95997 (11)0.0162 (3)
H14A0.30390.50320.93610.019*
H14B0.38050.44271.03740.019*
C150.24059 (12)0.36724 (12)0.94326 (12)0.0207 (3)
H15A0.17860.39810.95980.025*
H15B0.26740.31270.99310.025*
C160.19855 (12)0.33083 (11)0.82632 (12)0.0200 (3)
H16A0.23370.26850.82260.024*
H16B0.11690.32120.80240.024*
C170.22634 (11)0.40230 (10)0.75142 (12)0.0159 (3)
H17A0.19590.46590.75890.019*
H17B0.19160.38140.67570.019*
C180.49755 (11)0.35697 (10)0.94887 (11)0.0132 (3)
C190.63991 (11)0.25860 (11)0.92685 (12)0.0184 (3)
H19A0.65030.21960.86860.022*
H19B0.62030.21480.97640.022*
C200.74791 (12)0.30819 (10)0.98754 (12)0.0171 (3)
C210.80837 (13)0.35436 (11)0.93193 (13)0.0226 (3)
H210.78030.35640.85550.027*
C220.90963 (13)0.39735 (12)0.98804 (15)0.0272 (4)
H220.95060.42850.94980.033*
C230.95114 (13)0.39495 (12)1.09955 (15)0.0285 (4)
H231.02070.42401.13760.034*
C240.89110 (13)0.35018 (11)1.15538 (14)0.0250 (3)
H240.91910.34891.23180.030*
C250.78982 (12)0.30711 (11)1.09960 (12)0.0198 (3)
H250.74870.27661.13830.024*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0323 (5)0.0394 (6)0.0246 (5)0.0208 (5)−0.0003 (4)−0.0068 (5)
F20.0495 (7)0.0708 (9)0.0172 (5)0.0375 (6)0.0061 (5)0.0128 (5)
F30.0158 (5)0.0440 (7)0.0709 (9)0.0006 (4)−0.0062 (5)−0.0050 (6)
F40.0241 (4)0.0307 (5)0.0174 (5)−0.0109 (4)0.0059 (4)−0.0066 (4)
F50.0312 (5)0.0347 (5)0.0181 (5)0.0039 (4)0.0130 (4)−0.0075 (4)
F60.0283 (5)0.0250 (5)0.0139 (4)−0.0012 (4)0.0079 (4)0.0029 (4)
O10.0231 (5)0.0152 (5)0.0116 (5)0.0010 (4)0.0020 (4)−0.0035 (4)
O20.0150 (5)0.0235 (5)0.0129 (5)0.0064 (4)0.0045 (4)−0.0003 (4)
O30.0198 (5)0.0188 (5)0.0097 (5)0.0005 (4)0.0025 (4)0.0007 (4)
N10.0155 (5)0.0164 (6)0.0118 (6)−0.0008 (4)0.0040 (4)0.0003 (5)
N20.0146 (5)0.0171 (6)0.0077 (5)0.0022 (4)0.0038 (4)−0.0003 (4)
C10.0152 (6)0.0168 (7)0.0136 (7)−0.0004 (5)0.0031 (5)0.0007 (5)
C20.0162 (6)0.0167 (7)0.0130 (7)0.0004 (5)0.0049 (5)−0.0013 (5)
C30.0148 (6)0.0139 (7)0.0117 (7)−0.0034 (5)0.0043 (5)−0.0001 (5)
C40.0145 (6)0.0133 (6)0.0119 (6)−0.0017 (5)0.0052 (5)0.0007 (5)
C50.0155 (6)0.0172 (7)0.0126 (7)−0.0006 (5)0.0030 (5)0.0026 (5)
C60.0156 (6)0.0181 (7)0.0215 (8)0.0023 (5)0.0062 (6)0.0019 (6)
C70.0204 (7)0.0160 (7)0.0204 (8)0.0000 (6)0.0111 (6)−0.0014 (6)
C80.0172 (6)0.0142 (6)0.0139 (7)−0.0040 (5)0.0064 (5)−0.0021 (5)
C90.0144 (6)0.0127 (6)0.0129 (7)−0.0025 (5)0.0052 (5)−0.0002 (5)
C100.0222 (7)0.0291 (8)0.0149 (7)0.0065 (6)0.0012 (6)−0.0028 (6)
C110.0207 (7)0.0223 (8)0.0156 (7)−0.0029 (6)0.0090 (6)−0.0037 (6)
C120.0135 (6)0.0155 (7)0.0105 (7)−0.0001 (5)0.0027 (5)−0.0003 (5)
C130.0140 (6)0.0148 (6)0.0093 (6)0.0000 (5)0.0028 (5)−0.0010 (5)
C140.0183 (6)0.0189 (7)0.0135 (7)0.0029 (5)0.0082 (5)−0.0010 (5)
C150.0205 (7)0.0251 (8)0.0199 (8)0.0012 (6)0.0112 (6)0.0025 (6)
C160.0173 (7)0.0222 (8)0.0201 (8)−0.0037 (6)0.0059 (6)0.0029 (6)
C170.0133 (6)0.0187 (7)0.0144 (7)−0.0003 (5)0.0032 (5)0.0014 (5)
C180.0155 (6)0.0131 (6)0.0109 (7)−0.0017 (5)0.0044 (5)−0.0012 (5)
C190.0181 (7)0.0172 (7)0.0179 (7)0.0052 (6)0.0037 (5)−0.0020 (6)
C200.0164 (6)0.0132 (7)0.0200 (8)0.0056 (5)0.0040 (5)−0.0013 (6)
C210.0261 (8)0.0201 (8)0.0214 (8)0.0027 (6)0.0080 (6)−0.0016 (6)
C220.0260 (8)0.0214 (8)0.0367 (10)−0.0043 (6)0.0140 (7)−0.0027 (7)
C230.0211 (7)0.0214 (8)0.0376 (10)−0.0011 (6)0.0031 (7)−0.0067 (7)
C240.0252 (8)0.0205 (8)0.0217 (8)0.0053 (6)−0.0017 (6)−0.0021 (6)
C250.0204 (7)0.0179 (7)0.0187 (8)0.0051 (6)0.0034 (6)0.0019 (6)
Geometric parameters (Å, º) top
F1—C101.3284 (19)C8—C111.500 (2)
F2—C101.3289 (19)C12—C131.5500 (19)
F3—C101.339 (2)C12—H121.0000
F4—C111.3485 (17)C13—C171.5335 (18)
F5—C111.3407 (16)C13—H131.0000
F6—C111.3443 (18)C14—C151.529 (2)
O1—C121.4159 (17)C14—H14A0.9900
O1—H1O0.840 (9)C14—H14B0.9900
O2—C181.3570 (16)C15—C161.539 (2)
O2—C191.4600 (16)C15—H15A0.9900
O3—C181.2218 (17)C15—H15B0.9900
N1—C11.3176 (18)C16—C171.532 (2)
N1—C91.3615 (17)C16—H16A0.9900
N2—C181.3492 (17)C16—H16B0.9900
N2—C131.4733 (17)C17—H17A0.9900
N2—C141.4736 (16)C17—H17B0.9900
C1—C21.402 (2)C19—C201.508 (2)
C1—C101.508 (2)C19—H19A0.9900
C2—C31.3760 (19)C19—H19B0.9900
C2—H20.9500C20—C211.394 (2)
C3—C41.4250 (19)C20—C251.392 (2)
C3—C121.5100 (19)C21—C221.389 (2)
C4—C51.4223 (19)C21—H210.9500
C4—C91.4266 (19)C22—C231.386 (3)
C5—C61.363 (2)C22—H220.9500
C5—H50.9500C23—C241.383 (2)
C6—C71.413 (2)C23—H230.9500
C6—H60.9500C24—C251.389 (2)
C7—C81.367 (2)C24—H240.9500
C7—H70.9500C25—H250.9500
C8—C91.4288 (19)
C12—O1—H1O111.6 (13)N2—C13—H13108.1
C18—O2—C19115.08 (11)C17—C13—H13108.1
C1—N1—C9116.48 (12)C12—C13—H13108.1
C18—N2—C13122.22 (11)N2—C14—C15109.92 (11)
C18—N2—C14117.92 (11)N2—C14—H14A109.7
C13—N2—C14116.21 (11)C15—C14—H14A109.7
N1—C1—C2125.58 (13)N2—C14—H14B109.7
N1—C1—C10114.54 (12)C15—C14—H14B109.7
C2—C1—C10119.77 (12)H14A—C14—H14B108.2
C3—C2—C1118.75 (13)C14—C15—C16110.48 (11)
C3—C2—H2120.6C14—C15—H15A109.6
C1—C2—H2120.6C16—C15—H15A109.6
C2—C3—C4118.39 (12)C14—C15—H15B109.6
C2—C3—C12119.48 (12)C16—C15—H15B109.6
C4—C3—C12122.08 (12)H15A—C15—H15B108.1
C3—C4—C5123.78 (13)C17—C16—C15110.75 (12)
C3—C4—C9117.62 (12)C17—C16—H16A109.5
C5—C4—C9118.60 (12)C15—C16—H16A109.5
C6—C5—C4120.76 (13)C17—C16—H16B109.5
C6—C5—H5119.6C15—C16—H16B109.5
C4—C5—H5119.6H16A—C16—H16B108.1
C5—C6—C7120.77 (13)C16—C17—C13109.86 (11)
C5—C6—H6119.6C16—C17—H17A109.7
C7—C6—H6119.6C13—C17—H17A109.7
C8—C7—C6120.40 (13)C16—C17—H17B109.7
C8—C7—H7119.8C13—C17—H17B109.7
C6—C7—H7119.8H17A—C17—H17B108.2
C7—C8—C9120.34 (13)O3—C18—N2125.34 (12)
C7—C8—C11120.33 (13)O3—C18—O2122.70 (12)
C9—C8—C11119.31 (12)N2—C18—O2111.96 (11)
N1—C9—C4123.10 (12)O2—C19—C20112.88 (12)
N1—C9—C8117.80 (12)O2—C19—H19A109.0
C4—C9—C8119.10 (12)C20—C19—H19A109.0
F2—C10—F1107.32 (14)O2—C19—H19B109.0
F2—C10—F3106.66 (14)C20—C19—H19B109.0
F1—C10—F3106.61 (13)H19A—C19—H19B107.8
F2—C10—C1112.90 (13)C21—C20—C25119.02 (14)
F1—C10—C1112.91 (12)C21—C20—C19120.30 (14)
F3—C10—C1110.05 (13)C25—C20—C19120.68 (13)
F5—C11—F6106.16 (11)C22—C21—C20120.15 (15)
F5—C11—F4106.16 (12)C22—C21—H21119.9
F6—C11—F4106.48 (12)C20—C21—H21119.9
F5—C11—C8111.76 (12)C23—C22—C21120.35 (15)
F6—C11—C8113.08 (12)C23—C22—H22119.8
F4—C11—C8112.69 (11)C21—C22—H22119.8
O1—C12—C3107.77 (11)C24—C23—C22119.87 (15)
O1—C12—C13111.73 (11)C24—C23—H23120.1
C3—C12—C13109.35 (11)C22—C23—H23120.1
O1—C12—H12109.3C23—C24—C25119.97 (15)
C3—C12—H12109.3C23—C24—H24120.0
C13—C12—H12109.3C25—C24—H24120.0
N2—C13—C17109.02 (10)C24—C25—C20120.64 (14)
N2—C13—C12110.44 (11)C24—C25—H25119.7
C17—C13—C12113.07 (11)C20—C25—H25119.7
C9—N1—C1—C2−0.3 (2)C9—C8—C11—F4−63.18 (18)
C9—N1—C1—C10−176.49 (12)C2—C3—C12—O1−24.67 (16)
N1—C1—C2—C3−2.3 (2)C4—C3—C12—O1157.75 (12)
C10—C1—C2—C3173.71 (13)C2—C3—C12—C1396.96 (15)
C1—C2—C3—C42.6 (2)C4—C3—C12—C13−80.62 (15)
C1—C2—C3—C12−175.10 (12)C18—N2—C13—C17136.12 (13)
C2—C3—C4—C5178.88 (13)C14—N2—C13—C17−21.86 (16)
C12—C3—C4—C5−3.5 (2)C18—N2—C13—C12−99.08 (14)
C2—C3—C4—C9−0.51 (19)C14—N2—C13—C12102.94 (13)
C12—C3—C4—C9177.10 (12)O1—C12—C13—N2−67.05 (13)
C3—C4—C5—C6−177.76 (13)C3—C12—C13—N2173.73 (10)
C9—C4—C5—C61.6 (2)O1—C12—C13—C1755.41 (15)
C4—C5—C6—C7−0.7 (2)C3—C12—C13—C17−63.81 (14)
C5—C6—C7—C8−0.4 (2)C18—N2—C14—C15−94.29 (15)
C6—C7—C8—C90.6 (2)C13—N2—C14—C1564.67 (15)
C6—C7—C8—C11−178.42 (13)N2—C14—C15—C16−37.26 (16)
C1—N1—C9—C42.5 (2)C14—C15—C16—C17−23.02 (16)
C1—N1—C9—C8−177.60 (12)C15—C16—C17—C1365.54 (15)
C3—C4—C9—N1−2.2 (2)N2—C13—C17—C16−41.29 (15)
C5—C4—C9—N1178.41 (12)C12—C13—C17—C16−164.53 (12)
C3—C4—C9—C8177.97 (12)C13—N2—C18—O3−165.29 (13)
C5—C4—C9—C8−1.45 (19)C14—N2—C18—O3−7.7 (2)
C7—C8—C9—N1−179.50 (13)C13—N2—C18—O215.20 (18)
C11—C8—C9—N1−0.48 (19)C14—N2—C18—O2172.82 (11)
C7—C8—C9—C40.4 (2)C19—O2—C18—O37.38 (19)
C11—C8—C9—C4179.39 (12)C19—O2—C18—N2−173.10 (11)
N1—C1—C10—F2−38.11 (19)C18—O2—C19—C20−82.15 (15)
C2—C1—C10—F2145.43 (15)O2—C19—C20—C21−75.11 (16)
N1—C1—C10—F1−160.08 (13)O2—C19—C20—C25106.09 (15)
C2—C1—C10—F123.5 (2)C25—C20—C21—C220.9 (2)
N1—C1—C10—F380.93 (17)C19—C20—C21—C22−177.93 (14)
C2—C1—C10—F3−95.52 (16)C20—C21—C22—C23−0.2 (2)
C7—C8—C11—F5−3.62 (19)C21—C22—C23—C24−0.5 (2)
C9—C8—C11—F5177.36 (12)C22—C23—C24—C250.5 (2)
C7—C8—C11—F6−123.34 (14)C23—C24—C25—C200.2 (2)
C9—C8—C11—F657.64 (16)C21—C20—C25—C24−0.9 (2)
C7—C8—C11—F4115.84 (14)C19—C20—C25—C24177.91 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1o···O3i0.84 (1)1.90 (1)2.7294 (14)172 (2)
Symmetry code: (i) −x+1, −y+1, −z+2.

Experimental details

Crystal data
Chemical formulaC25H22F6N2O3
Mr512.45
Crystal system, space groupMonoclinic, P21/n
Temperature (K)100
a, b, c (Å)12.7793 (5), 13.9970 (7), 13.2188 (9)
β (°) 109.999 (8)
V (Å3)2221.9 (2)
Z4
Radiation typeMo Kα
µ (mm−1)0.13
Crystal size (mm)0.15 × 0.11 × 0.04
Data collection
DiffractometerRigaku Saturn724+
Absorption correctionMulti-scan
(CrystalClear-SM Expert; Rigaku, 2011)
Tmin, Tmax0.757, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections		10271, 5060, 4132
Rint0.026
(sin θ/λ)max (Å−1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.107, 1.00
No. of reflections5060
No. of parameters328
No. of restraints1
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.34, −0.32

Computer programs: CrystalClear-SM Expert (Rigaku, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and DIAMOND (Brandenburg, 2006), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1o···O3i0.840 (14)1.895 (14)2.7294 (14)172.1 (17)
Symmetry code: (i) −x+1, −y+1, −z+2.
 

Footnotes

‡Additional correspondence author, e-mail: j.wardell@abdn.ac.uk.

Acknowledgements

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES and FAPEMIG (Brazil).

References

First citationBrandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.  Google Scholar
 First citationCremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.  CrossRef CAS Web of Science Google Scholar
 First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
 First citationGonçalves, R. S. B., Souza, M. V. N. de, Wardell, J. L., Wardell, S. M. S. V. & Tiekink, E. R. T. (2011a). Acta Cryst. E67, o3315–o3316.  Web of Science CSD CrossRef IUCr Journals Google Scholar
 First citationGonçalves, R. S. B., Kaiser, C. R., Souza, M. V. N. de, Wardell, J. L., Wardell, S. M. S. V. & Tiekink, E. R. T. (2011b). Acta Cryst. E67, o1656–o1657.  Web of Science CSD CrossRef IUCr Journals Google Scholar
 First citationGonçalves, R. S. B., Kaiser, C. R., Lourenço, M. C. S., de Souza, M. V. N., Wardell, J. L., Wardell, S. M. S. V. & da Silva, A. D. (2010). Eur. J. Med. Chem. 45, 6095–6100.  Web of Science PubMed Google Scholar
 First citationGrellepois, F., Grellier, P., Bonnet-Delpon, D. & Bégué, J. P. (2005). ChemBioChem, 6, 648–652.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationMaguire, J. D., Krisin, Marwoto, H., Richie, T. L., Fryauff, D. J. & Baird, J. K. (2006). Clin. Infect. Dis. 42, 1067–1072.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationMao, J., Wang, Y., Wan, B., Kozikowski, A. P. S. G. & Franzblau, S. G. (2007). ChemMedChem, 2, 1624–1630.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationPitaluga, A. Jr, Prado, L. D., Seiceira, R., Wardell, J. L. & Wardell, S. M. S. V. (2010). Int. J. Pharm. 398, 50–60.  Web of Science CSD CrossRef CAS PubMed Google Scholar
 First citationRigaku (2011). CrystalClear-SM Expert. Rigaku Corporation, Tokyo, Japan.  Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationWardell, J. L., de Souza, M. V. N., Wardell, S. M. S. V. & Lourenço, M. C. S. (2011a). J. Mol. Struct. 990, 67–74.  Web of Science CSD CrossRef CAS Google Scholar
 First citationWardell, S. M. S. V., Wardell, J. L., Skakle, J. M. S. & Tiekink, E. R. T. (2011b). Z. Kristallogr. 226, 68–77.  Web of Science CSD CrossRef CAS Google Scholar
 First citationWardell, J. L., Wardell, S. M. S. V., Tiekink, E. R. T. & Lima, G. M. de (2010). Acta Cryst. E66, m336–m337.  Web of Science CSD CrossRef IUCr Journals Google Scholar
 First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 12| December 2011| Pages o3313-o3314
https://doi.org/10.1107/S1600536811047738
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS