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

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ISSN: 2056-9890

1,3-Di­cyclo­hexyl­imidazolidine-2,4,5-trione

aDepartment of Chemistry, University of Aveiro, QOPNA, 3810-193 Aveiro, Portugal, and bDepartment of Chemistry, University of Aveiro, CICECO, 3810-193 Aveiro, Portugal
*Correspondence e-mail: artur.silva@ua.pt, filipe.paz@ua.pt

(Received 29 October 2011; accepted 2 November 2011; online 9 November 2011)

The title compound, C15H22N2O3, has been isolated as a by-product of an oxidative cleavage of the C—C bond linking two five-membered rings of 1,3-dicyclo­hexyl-5-(3-oxo-2,3-dihydro­benzofuran-2-yl)imidazolidine-2,4-dione. Individual mol­ecular units are engaged in weak C=O⋯C=O inter­actions [O⋯C = 2.814 (10) and 2.871 (11) Å], leading to the formation of supra­molecular chains which close pack, mediated by van der Waals contacts, in the bc plane.

Related literature

For the synthesis of parabanic acid and its derivatives, see: Murray (1957[Murray, J. I. (1957). Org. Synth. 37, 71.], 1963[Murray, J. I. (1963). Org. Synth. Coll. 4, 744.]); Ulrichan & Sayigh (1965[Ulrichan, H. & Sayigh, D. A. A. R. (1965). J. Org. Chem. 30, 2781-2783.]); Richter et al. (1984[Richter, R., Stuber, F. A. & Tucker, B. (1984). J. Org. Chem. 49, 3675-3681.]); Orazi et al. (1977[Orazi, O. O., Corral, R. A. & Zinczuk, J. (1977). Synthesis, pp. 641-642.]); Zarzyka-Niemiec & Lubczak (2004[Zarzyka-Niemiec, I. & Lubczak, J. (2004). J. Appl. Polym. Sci. 94, 317-326.]). For biological applications of parabanic acid and its derivatives, see: Ishii et al. (1991[Ishii, A., Yamakawa, M. & Toyomaki, Y. (1991). US Patent No. 4 985 453.]); Kotani et al. (1997[Kotani, T., Nagaki, Y. & Okamoto, K. (1997). US Patent No. 4 096 130.]); Sato et al. (2011[Sato, T., Komine, T., Nomura, M., Rembutsu, M. & Kobayashi, N. (2011). Application No. WO2010 JP73460.]). For the synthesis, characterization and biological studies of the title compound, see: Xia et al. (2011[Xia, G., Benmohamed, R., Kim, J., Arvanites, A. C., Morimoto, R. I., Ferrante, R. J., Kirsch, D. R. & Silverman, R. B. (2011). J. Med. Chem. 54, 2409-2421.]). For general background to crystallographic studies of compounds having biological activity from our research group, see: Fernandes et al. (2010[Fernandes, J. A., Almeida Paz, F. A., Vilela, S. M. F., Tomé, J. C., Cavaleiro, J. A. S., Ribeiro-Claro, P. J. A. & Rocha, J. (2010). Acta Cryst. E66, o2271-o2272.], 2011[Fernandes, J. A., Almeida Paz, F. A., Marques, J., Marques, M. P. M. & Braga, S. S. (2011). Acta Cryst. C67, o57-o59.]); Loughzail et al. (2011[Loughzail, M., Fernandes, J. A., Baouid, A., Essaber, M., Cavaleiro, J. A. S. & Almeida Paz, F. A. (2011). Acta Cryst. E67, o2075-o2076.]). For the synthesis of a precursor mol­ecule, see: Talhi et al. (2011[Talhi, O., Silva, A. M. S., Pinto, D. C. G. A. & Paz, F. A. A. (2011). Unpublished results.]).

[Scheme 1]

Experimental

Crystal data
  • C15H22N2O3

  • Mr = 278.35

  • Orthorhombic, P 21 21 21

  • a = 6.5539 (8) Å

  • b = 11.5029 (15) Å

  • c = 19.524 (3) Å

  • V = 1471.9 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 150 K

  • 0.05 × 0.03 × 0.02 mm

Data collection
  • Bruker X8 KappaCCD APEXII diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 1997[Sheldrick, G. M. (1997). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.996, Tmax = 0.998

  • 8292 measured reflections

  • 1558 independent reflections

  • 1028 reflections with I > 2σ(I)

  • Rint = 0.047

Refinement
  • R[F2 > 2σ(F2)] = 0.106

  • wR(F2) = 0.320

  • S = 1.06

  • 1558 reflections

  • 181 parameters

  • 72 restraints

  • H-atom parameters constrained

  • Δρmax = 0.74 e Å−3

  • Δρmin = −0.42 e Å−3

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2. Bruker AXS, Delft, The Netherlands.Adv. Synth. Catal. 346, 171-184.]); cell refinement: SAINT-Plus (Bruker, 2005[Bruker (2005). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg, 2009[Brandenburg, K. (2009). DIAMOND. Crystal Impact GbR, Bonn, Germany.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

From the old literature we emphasize a handful of descriptions reporting the synthesis of parabanic acid (imidazolidine-2,4,5-trione, 1, Fig. 1) and derivatives. Among the reported synthetic methodologies, this heterocyclic compound can be prepared by the condensation of urea with diethyl oxalate in an ethanolic solution of sodium ethoxide (Murray, 1957; 1963). The synthesis of 1,3-disubstituted parabanic acid derivatives have been reported in a similar fashion, starting from 1,3-dialkylureas and following different pathways. The reaction of oxalyl chloride with 1,3-dialkylureas affords the 1,3-disubstituted parabanic skeleton upon cyclization. In other cases, the action of oxalyl chloride on carbodiimides has led to 2,2-dichloro-1,3-disubstituted imidazolidine-4,5-diones, which produced the parabanic structure after hydrolysis (Ulrichan & Sayigh, 1965). Furthermore, 3-substituted-5,5-dichlorooxazolidine-2,4-diones were obtained from the reaction of alkyl, aryl, and benzyl isocyanates with oxalyl chloride, giving in high yields the corresponding imidazolidine-2,4,5-triones after treatment with aniline (Richter et al., 1984). The selectivity of the direct mono- and di-N-substitution of parabanic acid has also been discussed in the literature (Orazi et al., 1977; Zarzyka-Niemiec & Lubczak, 2004). Concerning biological applications, several novel patented forms of parabanic acid derivatives and salts have shown interesting activities such as human AMPK activating, blood glucose-lowering and in vivo lipid-lowering activities. In this context, several therapeutic agents containing these compounds as the active principle are, for example, useful drugs in the treatment of diabetic complications (Sato et al., 2011; Kotani et al., 1997; Ishii et al., 1991). In the present study, we describe the crystal structure of 1,3-dicyclohexylparabanic acid (3) (Fig. 1) (Ulrichan & Sayigh, 1965) which has been isolated via a completely different procedure which consists of an oxidative cleavage of the C2'—C5 single bond of 1,3-dicyclohexyl-(3-oxo-2,3-dihydrobenzofuran-2-yl)imidazolidine-2,4-dione (2) (Fig. 1), previously prepared in a two-step reaction involving the action of dicyclohexylcarbodiimide (DCC) on chromone-2-carboxylic acid (Talhi et al., unpublished data).

The title compound (3) has recently been prepared and tested against cell lines modeling amyotrophic lateral sclerosis (Xia et al., 2011), but its crystal structure remains unpublished. Following our interest on the structural features of compounds with biological activity (Fernandes et al., 2010, 2011; Loughzail et al. 2011) here we wish to report the crystal structure of (3).

The asymmetric unit comprises a whole molecule (3, Fig. 2). The two cyclohexane substituent groups appear to exhibit chair conformations and their medium planes are almost perpendicular (ca 81 and 87°) with the medium plane of the central imidazolidine ring. The crystal packing is mainly driven by the need to effectively fill the available space in conjunction with several weak interactions, namely CO···CO: one O2 atom interacts with two vicinal carbonyl carbon atoms (C2 and C3) of a neighboring molecule [dO···C of 2.814 (10) and 2.871 (11) Å, dashed green lines in Fig. 3]. These weak interactions contribute to the formation of a zigzag columnar arrangement of the molecular units parallel to the a axis of the unit cell. Columns close pack in the bc plane in a typical brick-wall type fashion (Fig. 4).

Related literature top

For the synthesis of parabanic acid and its derivatives, see: Murray (1957, 1963); Ulrichan & Sayigh (1965); Richter et al. (1984); Orazi et al. (1977); Zarzyka-Niemiec & Lubczak (2004). For biological applications of parabanic acid and its derivatives, see: Ishii et al. (1991); Kotani et al. (1997); Sato et al. (2011). For the synthesis, characterization and biological studies of the title compound, see: Xia et al. (2011). For general background to crystallographic studies of compounds having biological activity from our research group, see: Fernandes et al. (2010, 2011); Loughzail et al. (2011). For the synthesis of a precursor molecule, see: Talhi et al. (2011).

Experimental top

NMR spectra were recorded on a Bruker Avance 300 spectrometer (300.13 for 1H and 75.47 MHz for 13C), with CDCl3 used as solvent. Chemical shifts (δ) are reported in p.p.m. and coupling constants (J) in Hz. The internal standard was TMS. Unequivocal 13C assignments have been performed with the aid of two-dimensional HSQC and HMBC experiments (delays for one bond and long-range JC/H couplings were optimized for 145 and 7 Hz, respectively).

All chemicals were purchased from commercial sources and used as received. 1,3-Dicyclohexyl-(3-oxo-2,3-dihydrobenzofuran-2-yl)imidazolidine-2,4-dione (2) was prepared according to the literature (Talhi et al., 2011).

Iodine (8.63 mg, 0.034 mmol dissolved in 1 ml of DMSO) was added to a solution of 2 (0.27 g, 0.681 mmol) in DMSO (2 ml). The reaction was refluxed in a sand bath for 30 minutes. After this period, the solution was poured into ice (5 g) and water (10 ml), leading to the formation of a yellow precipitate. The solid was collected by filtration, washed with water and dissolved in dichloromethane (30 ml). This organic solution was washed with a saturated sodium thiosulfate solution (2 × 200 ml) and finally purified by silica gel column chromatography using dichloromethane as eluent. The resulting compound was recrystallized from ethanol to give bright-yellow crystals of the title compound (Richter et al., 1984).

1,3-Dicyclohexylimidazolidine-2,4,5-trione, 3, C15H22N2O3 MW: 278.35 (0.033 g, yield 17 °). 1H NMR (300.13 MHz, CDCl3): δ = 1.24-2.28 (m, 20 H, —CH2—, H-2', H-2'', H-3', H-3'', H-4', H-4''), 4.00 (tt, J = 12.0, 3.7 Hz, 2H, H-1', H-1'') ppm. 13C NMR (75.47 MHz, CDCl3): δ = 25.1 (C-4', C-4''), 25.6 (C-3', C-3''), 29.5 (C-2', C-2''), 52.2 (C-1', C-1''), 153.3 (C-4, C-5), 153.8 (C-2) ppm.

Refinement top

Hydrogen atoms bound to carbon were placed in idealized positions with C—H = 1.00 (for methine-H) and 0.99 Å (for methylene-H). These atoms were included in the final structural model in riding-motion approximation with the isotropic thermal displacement parameters fixed at 1.2×Ueq of the carbon atom to which they are attached.

The cyclohexane rings are severely affected by disorder. Attempts to model this disorder proved to be unsuccessful hence, the large electron residual density surrounding these moieties: the largest peak and hole, 0.74 and -0.42 e.Å-3, are located at 0.92 and 0.40 Å, respectively, from the C10 atom.

In the absence of significant anomalous scattering effects, 1098 Friedel pairs were averaged in the final refinement.

Structure description top

From the old literature we emphasize a handful of descriptions reporting the synthesis of parabanic acid (imidazolidine-2,4,5-trione, 1, Fig. 1) and derivatives. Among the reported synthetic methodologies, this heterocyclic compound can be prepared by the condensation of urea with diethyl oxalate in an ethanolic solution of sodium ethoxide (Murray, 1957; 1963). The synthesis of 1,3-disubstituted parabanic acid derivatives have been reported in a similar fashion, starting from 1,3-dialkylureas and following different pathways. The reaction of oxalyl chloride with 1,3-dialkylureas affords the 1,3-disubstituted parabanic skeleton upon cyclization. In other cases, the action of oxalyl chloride on carbodiimides has led to 2,2-dichloro-1,3-disubstituted imidazolidine-4,5-diones, which produced the parabanic structure after hydrolysis (Ulrichan & Sayigh, 1965). Furthermore, 3-substituted-5,5-dichlorooxazolidine-2,4-diones were obtained from the reaction of alkyl, aryl, and benzyl isocyanates with oxalyl chloride, giving in high yields the corresponding imidazolidine-2,4,5-triones after treatment with aniline (Richter et al., 1984). The selectivity of the direct mono- and di-N-substitution of parabanic acid has also been discussed in the literature (Orazi et al., 1977; Zarzyka-Niemiec & Lubczak, 2004). Concerning biological applications, several novel patented forms of parabanic acid derivatives and salts have shown interesting activities such as human AMPK activating, blood glucose-lowering and in vivo lipid-lowering activities. In this context, several therapeutic agents containing these compounds as the active principle are, for example, useful drugs in the treatment of diabetic complications (Sato et al., 2011; Kotani et al., 1997; Ishii et al., 1991). In the present study, we describe the crystal structure of 1,3-dicyclohexylparabanic acid (3) (Fig. 1) (Ulrichan & Sayigh, 1965) which has been isolated via a completely different procedure which consists of an oxidative cleavage of the C2'—C5 single bond of 1,3-dicyclohexyl-(3-oxo-2,3-dihydrobenzofuran-2-yl)imidazolidine-2,4-dione (2) (Fig. 1), previously prepared in a two-step reaction involving the action of dicyclohexylcarbodiimide (DCC) on chromone-2-carboxylic acid (Talhi et al., unpublished data).

The title compound (3) has recently been prepared and tested against cell lines modeling amyotrophic lateral sclerosis (Xia et al., 2011), but its crystal structure remains unpublished. Following our interest on the structural features of compounds with biological activity (Fernandes et al., 2010, 2011; Loughzail et al. 2011) here we wish to report the crystal structure of (3).

The asymmetric unit comprises a whole molecule (3, Fig. 2). The two cyclohexane substituent groups appear to exhibit chair conformations and their medium planes are almost perpendicular (ca 81 and 87°) with the medium plane of the central imidazolidine ring. The crystal packing is mainly driven by the need to effectively fill the available space in conjunction with several weak interactions, namely CO···CO: one O2 atom interacts with two vicinal carbonyl carbon atoms (C2 and C3) of a neighboring molecule [dO···C of 2.814 (10) and 2.871 (11) Å, dashed green lines in Fig. 3]. These weak interactions contribute to the formation of a zigzag columnar arrangement of the molecular units parallel to the a axis of the unit cell. Columns close pack in the bc plane in a typical brick-wall type fashion (Fig. 4).

For the synthesis of parabanic acid and its derivatives, see: Murray (1957, 1963); Ulrichan & Sayigh (1965); Richter et al. (1984); Orazi et al. (1977); Zarzyka-Niemiec & Lubczak (2004). For biological applications of parabanic acid and its derivatives, see: Ishii et al. (1991); Kotani et al. (1997); Sato et al. (2011). For the synthesis, characterization and biological studies of the title compound, see: Xia et al. (2011). For general background to crystallographic studies of compounds having biological activity from our research group, see: Fernandes et al. (2010, 2011); Loughzail et al. (2011). For the synthesis of a precursor molecule, see: Talhi et al. (2011).

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT-Plus (Bruker, 2005); data reduction: SAINT-Plus (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. (Top). Molecular representation of imidazolidine-2,4,5-trione (1). (Bottom). Reaction scheme to isolate the title compound (3) from 1,3-dicyclohexyl-(3-oxo-2,3-dihydrobenzofuran-2-yl)imidazolidine-2,4-dione (2).
[Figure 2] Fig. 2. Asymmetric unit of the title compound. Displacement ellipsoids are drawn at the 50% probability level and the atomic labeling is provided for all non-hydrogen atoms. Hydrogen atoms are represented as small spheres with arbitrary radius.
[Figure 3] Fig. 3. Schematic representation of the weak CO···CO interactions (dashed green lines) connecting adjacent molecular units.
[Figure 4] Fig. 4. Perspective view of the crystal packing of the title compound viewed along the [100] direction of the unit cell.
1,3-Dicyclohexylimidazolidine-2,4,5-trione top
Crystal data top
C15H22N2O3F(000) = 600
Mr = 278.35Dx = 1.256 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 1312 reflections
a = 6.5539 (8) Åθ = 2.7–19.0°
b = 11.5029 (15) ŵ = 0.09 mm1
c = 19.524 (3) ÅT = 150 K
V = 1471.9 (3) Å3Block, yellow
Z = 40.05 × 0.03 × 0.02 mm
Data collection top
Bruker X8 KappaCCD APEXII
diffractometer
1558 independent reflections
Radiation source: fine-focus sealed tube1028 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.047
ω and φ scansθmax = 25.4°, θmin = 3.6°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1997)
h = 77
Tmin = 0.996, Tmax = 0.998k = 1310
8292 measured reflectionsl = 2323
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.106H-atom parameters constrained
wR(F2) = 0.320 w = 1/[σ2(Fo2) + (0.1747P)2 + 2.7021P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
1558 reflectionsΔρmax = 0.74 e Å3
181 parametersΔρmin = 0.42 e Å3
72 restraintsAbsolute structure: nd
Primary atom site location: structure-invariant direct methods
Crystal data top
C15H22N2O3V = 1471.9 (3) Å3
Mr = 278.35Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 6.5539 (8) ŵ = 0.09 mm1
b = 11.5029 (15) ÅT = 150 K
c = 19.524 (3) Å0.05 × 0.03 × 0.02 mm
Data collection top
Bruker X8 KappaCCD APEXII
diffractometer
1558 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1997)
1028 reflections with I > 2σ(I)
Tmin = 0.996, Tmax = 0.998Rint = 0.047
8292 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.10672 restraints
wR(F2) = 0.320H-atom parameters constrained
S = 1.06Δρmax = 0.74 e Å3
1558 reflectionsΔρmin = 0.42 e Å3
181 parametersAbsolute structure: nd
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. 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 > σ(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
N10.2051 (11)0.2826 (7)0.6061 (4)0.0494 (19)
N20.3789 (12)0.4457 (7)0.5865 (5)0.061 (2)
O10.4234 (13)0.3500 (10)0.6889 (4)0.103 (4)
O20.0437 (9)0.2643 (6)0.5014 (4)0.0559 (17)
O30.2667 (13)0.4828 (6)0.4759 (4)0.070 (2)
C10.3461 (15)0.3562 (10)0.6341 (5)0.056 (3)
C20.1559 (11)0.3133 (7)0.5403 (4)0.0366 (18)
C30.2743 (14)0.4269 (7)0.5262 (5)0.046 (2)
C40.128 (2)0.1759 (12)0.6392 (7)0.092 (4)
H40.06080.14630.59670.110*
C50.0635 (16)0.1903 (9)0.6766 (5)0.061 (3)
H5A0.16790.22130.64480.073*
H5B0.04300.24860.71330.073*
C60.143 (2)0.0794 (15)0.7083 (7)0.101 (4)
H6A0.19450.09890.75450.122*
H6B0.26150.05390.68080.122*
C70.014 (3)0.0147 (13)0.7150 (8)0.107 (5)
H7A0.09620.08430.70360.128*
H7B0.01910.02060.76440.128*
C80.1714 (19)0.0265 (11)0.6797 (6)0.075 (3)
H8A0.15370.08710.64420.091*
H8B0.27530.05520.71240.091*
C90.255 (2)0.0814 (9)0.6454 (6)0.078 (3)
H9A0.37750.10630.67120.094*
H9B0.30100.05930.59890.094*
C100.5293 (19)0.5375 (11)0.5983 (8)0.094 (4)
H100.57480.51340.64510.112*
C110.4542 (15)0.6494 (8)0.6151 (5)0.054 (2)
H11A0.37620.64290.65830.065*
H11B0.35680.67290.57890.065*
C120.6092 (17)0.7462 (9)0.6235 (6)0.066 (3)
H12A0.54680.81930.60700.080*
H12B0.63700.75590.67300.080*
C130.8030 (18)0.7306 (10)0.5885 (7)0.080 (3)
H13A0.79860.77950.54680.096*
H13B0.90970.76390.61850.096*
C140.8732 (18)0.6172 (11)0.5677 (7)0.083 (3)
H14A0.97970.59250.60060.099*
H14B0.94050.62580.52260.099*
C150.7265 (14)0.5231 (8)0.5621 (5)0.050 (2)
H15A0.79200.45130.57930.060*
H15B0.69700.51090.51280.060*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.034 (3)0.061 (5)0.054 (4)0.001 (4)0.008 (3)0.011 (4)
N20.034 (4)0.048 (5)0.101 (6)0.008 (3)0.002 (4)0.043 (5)
O10.077 (5)0.183 (10)0.049 (4)0.053 (6)0.018 (4)0.041 (5)
O20.043 (3)0.048 (4)0.077 (4)0.003 (3)0.011 (3)0.021 (3)
O30.090 (5)0.044 (4)0.075 (4)0.031 (4)0.034 (4)0.019 (3)
C10.041 (5)0.072 (7)0.056 (6)0.014 (5)0.005 (5)0.020 (5)
C20.028 (4)0.038 (4)0.044 (4)0.001 (3)0.007 (3)0.002 (3)
C30.046 (5)0.027 (4)0.063 (5)0.008 (4)0.007 (5)0.006 (4)
C40.061 (6)0.097 (8)0.118 (8)0.019 (6)0.030 (6)0.053 (7)
C50.051 (5)0.064 (6)0.066 (5)0.007 (5)0.015 (4)0.017 (5)
C60.067 (6)0.137 (9)0.100 (7)0.004 (7)0.025 (6)0.043 (7)
C70.120 (9)0.078 (7)0.122 (8)0.027 (7)0.034 (8)0.003 (7)
C80.073 (6)0.081 (7)0.073 (6)0.014 (6)0.005 (5)0.016 (5)
C90.079 (7)0.052 (6)0.103 (7)0.005 (6)0.035 (6)0.007 (5)
C100.061 (6)0.075 (7)0.145 (9)0.023 (6)0.017 (7)0.046 (7)
C110.049 (5)0.043 (5)0.071 (5)0.005 (4)0.013 (4)0.003 (4)
C120.062 (6)0.056 (6)0.080 (6)0.016 (5)0.011 (5)0.022 (5)
C130.070 (6)0.054 (6)0.117 (7)0.020 (5)0.027 (6)0.001 (6)
C140.050 (5)0.079 (7)0.119 (7)0.012 (5)0.016 (6)0.021 (6)
C150.037 (4)0.051 (5)0.061 (5)0.005 (4)0.005 (4)0.011 (4)
Geometric parameters (Å, º) top
N1—C11.367 (12)C8—C91.512 (16)
N1—C21.372 (10)C8—H8A0.9900
N1—C41.475 (14)C8—H8B0.9900
N2—C31.379 (12)C9—H9A0.9900
N2—C11.404 (14)C9—H9B0.9900
N2—C101.463 (13)C10—C111.416 (15)
O1—C11.185 (11)C10—C151.482 (15)
O2—C21.199 (10)C10—H101.0000
O3—C31.176 (10)C11—C121.516 (13)
C2—C31.544 (12)C11—H11A0.9900
C4—C91.373 (16)C11—H11B0.9900
C4—C51.464 (15)C12—C131.453 (16)
C4—H41.0000C12—H12A0.9900
C5—C61.510 (18)C12—H12B0.9900
C5—H5A0.9900C13—C141.442 (16)
C5—H5B0.9900C13—H13A0.9900
C6—C71.38 (2)C13—H13B0.9900
C6—H6A0.9900C14—C151.452 (14)
C6—H6B0.9900C14—H14A0.9900
C7—C81.405 (19)C14—H14B0.9900
C7—H7A0.9900C15—H15A0.9900
C7—H7B0.9900C15—H15B0.9900
C1—N1—C2111.9 (8)H8A—C8—H8B107.3
C1—N1—C4124.8 (9)C4—C9—C8118.0 (10)
C2—N1—C4123.0 (9)C4—C9—H9A107.8
C3—N2—C1112.0 (7)C8—C9—H9A107.8
C3—N2—C10125.6 (11)C4—C9—H9B107.8
C1—N2—C10121.9 (10)C8—C9—H9B107.8
O1—C1—N1127.8 (12)H9A—C9—H9B107.1
O1—C1—N2125.2 (11)C11—C10—N2117.3 (10)
N1—C1—N2107.0 (7)C11—C10—C15121.0 (10)
O2—C2—N1128.1 (8)N2—C10—C15115.5 (9)
O2—C2—C3126.5 (8)C11—C10—H1098.3
N1—C2—C3105.5 (7)N2—C10—H1098.3
O3—C3—N2130.5 (9)C15—C10—H1098.3
O3—C3—C2126.1 (9)C10—C11—C12117.3 (9)
N2—C3—C2103.3 (7)C10—C11—H11A108.0
C9—C4—C5124.4 (10)C12—C11—H11A108.0
C9—C4—N1119.4 (9)C10—C11—H11B108.0
C5—C4—N1114.6 (10)C12—C11—H11B108.0
C9—C4—H494.1H11A—C11—H11B107.2
C5—C4—H494.1C13—C12—C11116.4 (9)
N1—C4—H494.1C13—C12—H12A108.2
C4—C5—C6113.8 (10)C11—C12—H12A108.2
C4—C5—H5A108.8C13—C12—H12B108.2
C6—C5—H5A108.8C11—C12—H12B108.2
C4—C5—H5B108.8H12A—C12—H12B107.3
C6—C5—H5B108.8C14—C13—C12121.5 (9)
H5A—C5—H5B107.7C14—C13—H13A106.9
C7—C6—C5119.5 (11)C12—C13—H13A106.9
C7—C6—H6A107.4C14—C13—H13B106.9
C5—C6—H6A107.4C12—C13—H13B106.9
C7—C6—H6B107.4H13A—C13—H13B106.7
C5—C6—H6B107.4C13—C14—C15119.0 (9)
H6A—C6—H6B107.0C13—C14—H14A107.6
C6—C7—C8123.9 (13)C15—C14—H14A107.6
C6—C7—H7A106.4C13—C14—H14B107.6
C8—C7—H7A106.4C15—C14—H14B107.6
C6—C7—H7B106.4H14A—C14—H14B107.0
C8—C7—H7B106.4C14—C15—C10117.3 (8)
H7A—C7—H7B106.4C14—C15—H15A108.0
C7—C8—C9116.9 (12)C10—C15—H15A108.0
C7—C8—H8A108.1C14—C15—H15B108.0
C9—C8—H8A108.1C10—C15—H15B108.0
C7—C8—H8B108.1H15A—C15—H15B107.2
C9—C8—H8B108.1
C2—N1—C1—O1177.2 (9)C1—N1—C4—C595.6 (13)
C4—N1—C1—O12.9 (15)C2—N1—C4—C590.7 (13)
C2—N1—C1—N25.0 (10)C9—C4—C5—C616 (2)
C4—N1—C1—N2179.4 (8)N1—C4—C5—C6178.3 (11)
C3—N2—C1—O1177.6 (9)C4—C5—C6—C716 (2)
C10—N2—C1—O15.2 (15)C5—C6—C7—C817 (3)
C3—N2—C1—N14.6 (10)C6—C7—C8—C914 (2)
C10—N2—C1—N1177.0 (8)C5—C4—C9—C815 (2)
C1—N1—C2—O2177.1 (8)N1—C4—C9—C8179.9 (11)
C4—N1—C2—O22.6 (13)C7—C8—C9—C412.7 (19)
C1—N1—C2—C33.5 (9)C3—N2—C10—C1182.0 (15)
C4—N1—C2—C3178.0 (8)C1—N2—C10—C11106.7 (14)
C1—N2—C3—O3179.9 (9)C3—N2—C10—C1570.7 (15)
C10—N2—C3—O37.8 (15)C1—N2—C10—C15100.6 (13)
C1—N2—C3—C22.4 (9)N2—C10—C11—C12176.7 (11)
C10—N2—C3—C2174.4 (9)C15—C10—C11—C1225.6 (18)
O2—C2—C3—O32.2 (13)C10—C11—C12—C1323.8 (16)
N1—C2—C3—O3177.3 (9)C11—C12—C13—C1420.9 (19)
O2—C2—C3—N2179.9 (8)C12—C13—C14—C1519 (2)
N1—C2—C3—N20.6 (8)C13—C14—C15—C1019.0 (19)
C1—N1—C4—C970.9 (17)C11—C10—C15—C1423.2 (19)
C2—N1—C4—C9102.8 (14)N2—C10—C15—C14174.9 (11)

Experimental details

Crystal data
Chemical formulaC15H22N2O3
Mr278.35
Crystal system, space groupOrthorhombic, P212121
Temperature (K)150
a, b, c (Å)6.5539 (8), 11.5029 (15), 19.524 (3)
V3)1471.9 (3)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.05 × 0.03 × 0.02
Data collection
DiffractometerBruker X8 KappaCCD APEXII
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1997)
Tmin, Tmax0.996, 0.998
No. of measured, independent and
observed [I > 2σ(I)] reflections
8292, 1558, 1028
Rint0.047
(sin θ/λ)max1)0.602
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.106, 0.320, 1.06
No. of reflections1558
No. of parameters181
No. of restraints72
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.74, 0.42
Absolute structureNd

Computer programs: APEX2 (Bruker, 2006), SAINT-Plus (Bruker, 2005), SHELXTL (Sheldrick, 2008), DIAMOND (Brandenburg, 2009).

 

Acknowledgements

We are grateful to the Fundação para a Ciência e a Tecnologia (FCT/FEDER, Portugal) for their general financial support to QOPNA and CICECO, and for post-doctoral research grant No. SFRH/BPD/63736/2009 (to JAF). We also thank the (European Community's) Seventh Framework Programme (FP7/2007–20139 under grant agreement No. 215009). Thanks are also due to the FCT for specific funding toward the purchase of the single-crystal diffractometer.

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