organic compounds
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
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, 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
Crystal data
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Data collection: APEX2 (Bruker, 2006); cell SAINT-Plus (Bruker, 2005); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg, 2009); software used to prepare material for publication: SHELXTL.
Supporting information
https://doi.org/10.1107/S1600536811046253/tk5010sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811046253/tk5010Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536811046253/tk5010Isup3.cml
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
using dichloromethane as 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.
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
effects, 1098 Friedel pairs were averaged in the final refinement.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
In other cases, the action of oxalyl chloride on 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 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 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
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 of (3).The ═O···C═O: 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 Columns close pack in the bc plane in a typical brick-wall type fashion (Fig. 4).
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 CFor 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).
Data collection: APEX2 (Bruker, 2006); cell
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).C15H22N2O3 | F(000) = 600 |
Mr = 278.35 | Dx = 1.256 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1312 reflections |
a = 6.5539 (8) Å | θ = 2.7–19.0° |
b = 11.5029 (15) Å | µ = 0.09 mm−1 |
c = 19.524 (3) Å | T = 150 K |
V = 1471.9 (3) Å3 | Block, yellow |
Z = 4 | 0.05 × 0.03 × 0.02 mm |
Bruker X8 KappaCCD APEXII diffractometer | 1558 independent reflections |
Radiation source: fine-focus sealed tube | 1028 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.047 |
ω and φ scans | θmax = 25.4°, θmin = 3.6° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1997) | h = −7→7 |
Tmin = 0.996, Tmax = 0.998 | k = −13→10 |
8292 measured reflections | l = −23→23 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.106 | H-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 reflections | Δρmax = 0.74 e Å−3 |
181 parameters | Δρmin = −0.42 e Å−3 |
72 restraints | Absolute structure: nd |
Primary atom site location: structure-invariant direct methods |
C15H22N2O3 | V = 1471.9 (3) Å3 |
Mr = 278.35 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.5539 (8) Å | µ = 0.09 mm−1 |
b = 11.5029 (15) Å | T = 150 K |
c = 19.524 (3) Å | 0.05 × 0.03 × 0.02 mm |
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 = 0.998 | Rint = 0.047 |
8292 measured reflections |
R[F2 > 2σ(F2)] = 0.106 | 72 restraints |
wR(F2) = 0.320 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.74 e Å−3 |
1558 reflections | Δρmin = −0.42 e Å−3 |
181 parameters | Absolute structure: nd |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.2051 (11) | 0.2826 (7) | 0.6061 (4) | 0.0494 (19) | |
N2 | 0.3789 (12) | 0.4457 (7) | 0.5865 (5) | 0.061 (2) | |
O1 | 0.4234 (13) | 0.3500 (10) | 0.6889 (4) | 0.103 (4) | |
O2 | 0.0437 (9) | 0.2643 (6) | 0.5014 (4) | 0.0559 (17) | |
O3 | 0.2667 (13) | 0.4828 (6) | 0.4759 (4) | 0.070 (2) | |
C1 | 0.3461 (15) | 0.3562 (10) | 0.6341 (5) | 0.056 (3) | |
C2 | 0.1559 (11) | 0.3133 (7) | 0.5403 (4) | 0.0366 (18) | |
C3 | 0.2743 (14) | 0.4269 (7) | 0.5262 (5) | 0.046 (2) | |
C4 | 0.128 (2) | 0.1759 (12) | 0.6392 (7) | 0.092 (4) | |
H4 | 0.0608 | 0.1463 | 0.5967 | 0.110* | |
C5 | −0.0635 (16) | 0.1903 (9) | 0.6766 (5) | 0.061 (3) | |
H5A | −0.1679 | 0.2213 | 0.6448 | 0.073* | |
H5B | −0.0430 | 0.2486 | 0.7133 | 0.073* | |
C6 | −0.143 (2) | 0.0794 (15) | 0.7083 (7) | 0.101 (4) | |
H6A | −0.1945 | 0.0989 | 0.7545 | 0.122* | |
H6B | −0.2615 | 0.0539 | 0.6808 | 0.122* | |
C7 | −0.014 (3) | −0.0147 (13) | 0.7150 (8) | 0.107 (5) | |
H7A | −0.0962 | −0.0843 | 0.7036 | 0.128* | |
H7B | 0.0191 | −0.0206 | 0.7644 | 0.128* | |
C8 | 0.1714 (19) | −0.0265 (11) | 0.6797 (6) | 0.075 (3) | |
H8A | 0.1537 | −0.0871 | 0.6442 | 0.091* | |
H8B | 0.2753 | −0.0552 | 0.7124 | 0.091* | |
C9 | 0.255 (2) | 0.0814 (9) | 0.6454 (6) | 0.078 (3) | |
H9A | 0.3775 | 0.1063 | 0.6712 | 0.094* | |
H9B | 0.3010 | 0.0593 | 0.5989 | 0.094* | |
C10 | 0.5293 (19) | 0.5375 (11) | 0.5983 (8) | 0.094 (4) | |
H10 | 0.5748 | 0.5134 | 0.6451 | 0.112* | |
C11 | 0.4542 (15) | 0.6494 (8) | 0.6151 (5) | 0.054 (2) | |
H11A | 0.3762 | 0.6429 | 0.6583 | 0.065* | |
H11B | 0.3568 | 0.6729 | 0.5789 | 0.065* | |
C12 | 0.6092 (17) | 0.7462 (9) | 0.6235 (6) | 0.066 (3) | |
H12A | 0.5468 | 0.8193 | 0.6070 | 0.080* | |
H12B | 0.6370 | 0.7559 | 0.6730 | 0.080* | |
C13 | 0.8030 (18) | 0.7306 (10) | 0.5885 (7) | 0.080 (3) | |
H13A | 0.7986 | 0.7795 | 0.5468 | 0.096* | |
H13B | 0.9097 | 0.7639 | 0.6185 | 0.096* | |
C14 | 0.8732 (18) | 0.6172 (11) | 0.5677 (7) | 0.083 (3) | |
H14A | 0.9797 | 0.5925 | 0.6006 | 0.099* | |
H14B | 0.9405 | 0.6258 | 0.5226 | 0.099* | |
C15 | 0.7265 (14) | 0.5231 (8) | 0.5621 (5) | 0.050 (2) | |
H15A | 0.7920 | 0.4513 | 0.5793 | 0.060* | |
H15B | 0.6970 | 0.5109 | 0.5128 | 0.060* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.034 (3) | 0.061 (5) | 0.054 (4) | 0.001 (4) | 0.008 (3) | 0.011 (4) |
N2 | 0.034 (4) | 0.048 (5) | 0.101 (6) | −0.008 (3) | −0.002 (4) | −0.043 (5) |
O1 | 0.077 (5) | 0.183 (10) | 0.049 (4) | 0.053 (6) | −0.018 (4) | −0.041 (5) |
O2 | 0.043 (3) | 0.048 (4) | 0.077 (4) | 0.003 (3) | −0.011 (3) | −0.021 (3) |
O3 | 0.090 (5) | 0.044 (4) | 0.075 (4) | 0.031 (4) | 0.034 (4) | 0.019 (3) |
C1 | 0.041 (5) | 0.072 (7) | 0.056 (6) | 0.014 (5) | −0.005 (5) | −0.020 (5) |
C2 | 0.028 (4) | 0.038 (4) | 0.044 (4) | 0.001 (3) | −0.007 (3) | −0.002 (3) |
C3 | 0.046 (5) | 0.027 (4) | 0.063 (5) | 0.008 (4) | 0.007 (5) | −0.006 (4) |
C4 | 0.061 (6) | 0.097 (8) | 0.118 (8) | 0.019 (6) | 0.030 (6) | 0.053 (7) |
C5 | 0.051 (5) | 0.064 (6) | 0.066 (5) | −0.007 (5) | 0.015 (4) | −0.017 (5) |
C6 | 0.067 (6) | 0.137 (9) | 0.100 (7) | −0.004 (7) | 0.025 (6) | 0.043 (7) |
C7 | 0.120 (9) | 0.078 (7) | 0.122 (8) | −0.027 (7) | 0.034 (8) | −0.003 (7) |
C8 | 0.073 (6) | 0.081 (7) | 0.073 (6) | −0.014 (6) | −0.005 (5) | 0.016 (5) |
C9 | 0.079 (7) | 0.052 (6) | 0.103 (7) | −0.005 (6) | 0.035 (6) | −0.007 (5) |
C10 | 0.061 (6) | 0.075 (7) | 0.145 (9) | −0.023 (6) | 0.017 (7) | −0.046 (7) |
C11 | 0.049 (5) | 0.043 (5) | 0.071 (5) | −0.005 (4) | 0.013 (4) | −0.003 (4) |
C12 | 0.062 (6) | 0.056 (6) | 0.080 (6) | −0.016 (5) | 0.011 (5) | −0.022 (5) |
C13 | 0.070 (6) | 0.054 (6) | 0.117 (7) | −0.020 (5) | 0.027 (6) | −0.001 (6) |
C14 | 0.050 (5) | 0.079 (7) | 0.119 (7) | −0.012 (5) | 0.016 (6) | −0.021 (6) |
C15 | 0.037 (4) | 0.051 (5) | 0.061 (5) | 0.005 (4) | 0.005 (4) | −0.011 (4) |
N1—C1 | 1.367 (12) | C8—C9 | 1.512 (16) |
N1—C2 | 1.372 (10) | C8—H8A | 0.9900 |
N1—C4 | 1.475 (14) | C8—H8B | 0.9900 |
N2—C3 | 1.379 (12) | C9—H9A | 0.9900 |
N2—C1 | 1.404 (14) | C9—H9B | 0.9900 |
N2—C10 | 1.463 (13) | C10—C11 | 1.416 (15) |
O1—C1 | 1.185 (11) | C10—C15 | 1.482 (15) |
O2—C2 | 1.199 (10) | C10—H10 | 1.0000 |
O3—C3 | 1.176 (10) | C11—C12 | 1.516 (13) |
C2—C3 | 1.544 (12) | C11—H11A | 0.9900 |
C4—C9 | 1.373 (16) | C11—H11B | 0.9900 |
C4—C5 | 1.464 (15) | C12—C13 | 1.453 (16) |
C4—H4 | 1.0000 | C12—H12A | 0.9900 |
C5—C6 | 1.510 (18) | C12—H12B | 0.9900 |
C5—H5A | 0.9900 | C13—C14 | 1.442 (16) |
C5—H5B | 0.9900 | C13—H13A | 0.9900 |
C6—C7 | 1.38 (2) | C13—H13B | 0.9900 |
C6—H6A | 0.9900 | C14—C15 | 1.452 (14) |
C6—H6B | 0.9900 | C14—H14A | 0.9900 |
C7—C8 | 1.405 (19) | C14—H14B | 0.9900 |
C7—H7A | 0.9900 | C15—H15A | 0.9900 |
C7—H7B | 0.9900 | C15—H15B | 0.9900 |
C1—N1—C2 | 111.9 (8) | H8A—C8—H8B | 107.3 |
C1—N1—C4 | 124.8 (9) | C4—C9—C8 | 118.0 (10) |
C2—N1—C4 | 123.0 (9) | C4—C9—H9A | 107.8 |
C3—N2—C1 | 112.0 (7) | C8—C9—H9A | 107.8 |
C3—N2—C10 | 125.6 (11) | C4—C9—H9B | 107.8 |
C1—N2—C10 | 121.9 (10) | C8—C9—H9B | 107.8 |
O1—C1—N1 | 127.8 (12) | H9A—C9—H9B | 107.1 |
O1—C1—N2 | 125.2 (11) | C11—C10—N2 | 117.3 (10) |
N1—C1—N2 | 107.0 (7) | C11—C10—C15 | 121.0 (10) |
O2—C2—N1 | 128.1 (8) | N2—C10—C15 | 115.5 (9) |
O2—C2—C3 | 126.5 (8) | C11—C10—H10 | 98.3 |
N1—C2—C3 | 105.5 (7) | N2—C10—H10 | 98.3 |
O3—C3—N2 | 130.5 (9) | C15—C10—H10 | 98.3 |
O3—C3—C2 | 126.1 (9) | C10—C11—C12 | 117.3 (9) |
N2—C3—C2 | 103.3 (7) | C10—C11—H11A | 108.0 |
C9—C4—C5 | 124.4 (10) | C12—C11—H11A | 108.0 |
C9—C4—N1 | 119.4 (9) | C10—C11—H11B | 108.0 |
C5—C4—N1 | 114.6 (10) | C12—C11—H11B | 108.0 |
C9—C4—H4 | 94.1 | H11A—C11—H11B | 107.2 |
C5—C4—H4 | 94.1 | C13—C12—C11 | 116.4 (9) |
N1—C4—H4 | 94.1 | C13—C12—H12A | 108.2 |
C4—C5—C6 | 113.8 (10) | C11—C12—H12A | 108.2 |
C4—C5—H5A | 108.8 | C13—C12—H12B | 108.2 |
C6—C5—H5A | 108.8 | C11—C12—H12B | 108.2 |
C4—C5—H5B | 108.8 | H12A—C12—H12B | 107.3 |
C6—C5—H5B | 108.8 | C14—C13—C12 | 121.5 (9) |
H5A—C5—H5B | 107.7 | C14—C13—H13A | 106.9 |
C7—C6—C5 | 119.5 (11) | C12—C13—H13A | 106.9 |
C7—C6—H6A | 107.4 | C14—C13—H13B | 106.9 |
C5—C6—H6A | 107.4 | C12—C13—H13B | 106.9 |
C7—C6—H6B | 107.4 | H13A—C13—H13B | 106.7 |
C5—C6—H6B | 107.4 | C13—C14—C15 | 119.0 (9) |
H6A—C6—H6B | 107.0 | C13—C14—H14A | 107.6 |
C6—C7—C8 | 123.9 (13) | C15—C14—H14A | 107.6 |
C6—C7—H7A | 106.4 | C13—C14—H14B | 107.6 |
C8—C7—H7A | 106.4 | C15—C14—H14B | 107.6 |
C6—C7—H7B | 106.4 | H14A—C14—H14B | 107.0 |
C8—C7—H7B | 106.4 | C14—C15—C10 | 117.3 (8) |
H7A—C7—H7B | 106.4 | C14—C15—H15A | 108.0 |
C7—C8—C9 | 116.9 (12) | C10—C15—H15A | 108.0 |
C7—C8—H8A | 108.1 | C14—C15—H15B | 108.0 |
C9—C8—H8A | 108.1 | C10—C15—H15B | 108.0 |
C7—C8—H8B | 108.1 | H15A—C15—H15B | 107.2 |
C9—C8—H8B | 108.1 | ||
C2—N1—C1—O1 | −177.2 (9) | C1—N1—C4—C5 | 95.6 (13) |
C4—N1—C1—O1 | −2.9 (15) | C2—N1—C4—C5 | −90.7 (13) |
C2—N1—C1—N2 | 5.0 (10) | C9—C4—C5—C6 | −16 (2) |
C4—N1—C1—N2 | 179.4 (8) | N1—C4—C5—C6 | 178.3 (11) |
C3—N2—C1—O1 | 177.6 (9) | C4—C5—C6—C7 | 16 (2) |
C10—N2—C1—O1 | 5.2 (15) | C5—C6—C7—C8 | −17 (3) |
C3—N2—C1—N1 | −4.6 (10) | C6—C7—C8—C9 | 14 (2) |
C10—N2—C1—N1 | −177.0 (8) | C5—C4—C9—C8 | 15 (2) |
C1—N1—C2—O2 | 177.1 (8) | N1—C4—C9—C8 | 179.9 (11) |
C4—N1—C2—O2 | 2.6 (13) | C7—C8—C9—C4 | −12.7 (19) |
C1—N1—C2—C3 | −3.5 (9) | C3—N2—C10—C11 | 82.0 (15) |
C4—N1—C2—C3 | −178.0 (8) | C1—N2—C10—C11 | −106.7 (14) |
C1—N2—C3—O3 | −179.9 (9) | C3—N2—C10—C15 | −70.7 (15) |
C10—N2—C3—O3 | −7.8 (15) | C1—N2—C10—C15 | 100.6 (13) |
C1—N2—C3—C2 | 2.4 (9) | N2—C10—C11—C12 | −176.7 (11) |
C10—N2—C3—C2 | 174.4 (9) | C15—C10—C11—C12 | −25.6 (18) |
O2—C2—C3—O3 | 2.2 (13) | C10—C11—C12—C13 | 23.8 (16) |
N1—C2—C3—O3 | −177.3 (9) | C11—C12—C13—C14 | −20.9 (19) |
O2—C2—C3—N2 | −179.9 (8) | C12—C13—C14—C15 | 19 (2) |
N1—C2—C3—N2 | 0.6 (8) | C13—C14—C15—C10 | −19.0 (19) |
C1—N1—C4—C9 | −70.9 (17) | C11—C10—C15—C14 | 23.2 (19) |
C2—N1—C4—C9 | 102.8 (14) | N2—C10—C15—C14 | 174.9 (11) |
Experimental details
Crystal data | |
Chemical formula | C15H22N2O3 |
Mr | 278.35 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 150 |
a, b, c (Å) | 6.5539 (8), 11.5029 (15), 19.524 (3) |
V (Å3) | 1471.9 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.05 × 0.03 × 0.02 |
Data collection | |
Diffractometer | Bruker X8 KappaCCD APEXII |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1997) |
Tmin, Tmax | 0.996, 0.998 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8292, 1558, 1028 |
Rint | 0.047 |
(sin θ/λ)max (Å−1) | 0.602 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.106, 0.320, 1.06 |
No. of reflections | 1558 |
No. of parameters | 181 |
No. of restraints | 72 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.74, −0.42 |
Absolute structure | Nd |
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.
References
Brandenburg, K. (2009). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2005). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2006). APEX2. Bruker AXS, Delft, The Netherlands.Adv. Synth. Catal. 346, 171-184. Google Scholar
Fernandes, J. A., Almeida Paz, F. A., Marques, J., Marques, M. P. M. & Braga, S. S. (2011). Acta Cryst. C67, o57–o59. Web of Science CSD CrossRef IUCr Journals Google Scholar
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. Web of Science CSD CrossRef IUCr Journals Google Scholar
Ishii, A., Yamakawa, M. & Toyomaki, Y. (1991). US Patent No. 4 985 453. Google Scholar
Kotani, T., Nagaki, Y. & Okamoto, K. (1997). US Patent No. 4 096 130. Google Scholar
Loughzail, M., Fernandes, J. A., Baouid, A., Essaber, M., Cavaleiro, J. A. S. & Almeida Paz, F. A. (2011). Acta Cryst. E67, o2075–o2076. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Murray, J. I. (1957). Org. Synth. 37, 71. Google Scholar
Murray, J. I. (1963). Org. Synth. Coll. 4, 744. Google Scholar
Orazi, O. O., Corral, R. A. & Zinczuk, J. (1977). Synthesis, pp. 641–642. CrossRef Google Scholar
Richter, R., Stuber, F. A. & Tucker, B. (1984). J. Org. Chem. 49, 3675–3681. CSD CrossRef CAS Web of Science Google Scholar
Sato, T., Komine, T., Nomura, M., Rembutsu, M. & Kobayashi, N. (2011). Application No. WO2010 JP73460. Google Scholar
Sheldrick, G. M. (1997). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Talhi, O., Silva, A. M. S., Pinto, D. C. G. A. & Paz, F. A. A. (2011). Unpublished results. Google Scholar
Ulrichan, H. & Sayigh, D. A. A. R. (1965). J. Org. Chem. 30, 2781–2783. Google Scholar
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. Web of Science CrossRef CAS PubMed Google Scholar
Zarzyka-Niemiec, I. & Lubczak, J. (2004). J. Appl. Polym. Sci. 94, 317–326. CAS Google Scholar
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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 C═O···C═O: 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).