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Acta Crystallogr Sect E Struct Rep Online. 2010 August 1; 66(Pt 8): o2022.
Published online 2010 July 14. doi:  10.1107/S1600536810026929
PMCID: PMC3007345

(S)-3-Chloro-4-(4-ethyl­piperazin-1-yl)-5-[(1R,2S,5R)-2-isopropyl-5-methyl­cyclo­hex­yloxy]furan-2(5H)-one

Abstract

The title compound, C20H33ClN2O3, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dichloro-5-(S)-(l-menth­yloxy)furan-2(5H)-one and 1-ethyl­piperazine in the presence of potassium fluoride. The mol­ecular structure contains an approximately planar five-membered furan­one ring [maximum atomic deviation = 0.024 (2) Å] and two six-membered rings adopting chair conformations. Weak inter­molecular C—H(...)O hydrogen bonding is present in the crystal structure.

Related literature

The title compound is a 4-amino-2(5H)-furan­one derivative. For the biological activity of 4-amino-2(5H)-furan­ones, see: Kimura et al. (2000 [triangle]); Tanoury et al. (2008 [triangle]). For the asymmetric Michael addition reactions of 2(5H)-furan­ones, see: Bertrand et al. (2000 [triangle]); He et al. (2006 [triangle]); Sarma et al. (2007 [triangle]). For the synthesis of the title compound, see: Song et al. (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2022-scheme1.jpg

Experimental

Crystal data

  • C20H33ClN2O3
  • M r = 384.93
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2022-efi1.jpg
  • a = 8.7168 (15) Å
  • b = 10.1470 (18) Å
  • c = 24.478 (4) Å
  • V = 2165.1 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.20 mm−1
  • T = 298 K
  • 0.23 × 0.20 × 0.16 mm

Data collection

  • Bruker APEXII area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.956, T max = 0.969
  • 12202 measured reflections
  • 4384 independent reflections
  • 2730 reflections with I > 2σ(I)
  • R int = 0.045

Refinement

  • R[F 2 > 2σ(F 2)] = 0.046
  • wR(F 2) = 0.107
  • S = 1.01
  • 4384 reflections
  • 240 parameters
  • H-atom parameters constrained
  • Δρmax = 0.13 e Å−3
  • Δρmin = −0.17 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1866 Friedel pairs
  • Flack parameter: 0.00 (8)

Data collection: APEX2 (Bruker, 2008 [triangle]); cell refinement: SAINT (Bruker, 2008 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810026929/xu2787sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810026929/xu2787Isup2.hkl

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

Acknowledgments

The work was supported by the National Natural Science Foundation of China (grant No. 20772035) and the Natural Science Foundation of Guangdong Province, China (grant No. 5300082).

supplementary crystallographic information

Comment

With their poly-functional groups and highly active reactivity, 5-menthyloxy-2(5H)-furanones, serving as a kind of important building blocks, were widely used for the synthesis of a variety of chiral 5-menthyloxy-2(5H)-furanone derivatives. Until now, the asymmetric Michael addition reactions of 2(5H)-furanone with nucleophiles, to construct C-X (X=N, O, S, P, C) bond, have been a prominent objective in furanone chemistry (Bertrand et al., 2000; He et al., 2006; Sarma et al., 2007). At the same time, 4-amino-2(5H)-furanone is an attractive moiety in chemical, pharmaceutical and agrochemical research (Kimura et al., 2000; Tanoury et al., 2008).

Therefore we are interested in the tandem Michael addition-elimination reaction of the chiral synthon 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone and 1-ethylpiperazine in the present of potassium fluoride. The structure of the title compound (I) is illustrated in Fig. 1. The crystal structure of the title compound which has four chiral centers ( C4(S), C5(R), C6(S), C9(R)) contains a five-membered furanone ring and two six-membered rings connected each other via C4—O3—C5 ether bond and C3—N2 bond. The furanone ring of C2—C3—C4—O1—C1 is approximately planar, whereas the six-membered ring displays a chair conformation.

Experimental

The precursor 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone was prepared according to the literature procedure (Song et al., 2009). After the mixture of 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone (2.0 mmol) and potassium fluoride (6.0 mmol) was dissolved in absolute tetrahydrofuran(2.0 mL) under nitrogen atmosphere, tetrahydrofuran solution of 1-ethylpiperazine (3.0 mmol) was added. The reaction was carried out under the stirring at room temperature for 24 h. Once the reaction was complete, the solvents were removed under reduced pressure. The residual solid was dissolved in dichloromethane. Then the combined organic layers from extraction were concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography with the gradient mixture of petroleum ether and ethyl acetate to give the product yielding (I) 0.280 g (36.1%).

Refinement

H atoms were positioned in calculated positions with C—H = 0.93-0.98 Å and were refined using a riding model, with Uiso(H) = 1.5Ueq(C) for methyl and 1.2Ueq(C) for the others.

Figures

Fig. 1.
The molecular structure of the title compound showing the atom-labelling scheme. Ellipsoids are drawn at the 50% probability level.
Fig. 2.
Perspective view of the crystal packing.

Crystal data

C20H33ClN2O3F(000) = 832.0
Mr = 384.93Dx = 1.181 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 1893 reflections
a = 8.7168 (15) Åθ = 2.6–19.0°
b = 10.1470 (18) ŵ = 0.20 mm1
c = 24.478 (4) ÅT = 298 K
V = 2165.1 (6) Å3Block, colourless
Z = 40.23 × 0.20 × 0.16 mm

Data collection

Bruker APEXII area-detector diffractometer4384 independent reflections
Radiation source: fine-focus sealed tube2730 reflections with I > 2σ(I)
graphiteRint = 0.045
[var phi] and ω scanθmax = 26.3°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)h = −10→10
Tmin = 0.956, Tmax = 0.969k = −8→12
12202 measured reflectionsl = −30→30

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.107w = 1/[σ2(Fo2) + (0.0425P)2 + 0.0387P] where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max < 0.001
4384 reflectionsΔρmax = 0.13 e Å3
240 parametersΔρmin = −0.17 e Å3
0 restraintsAbsolute structure: Flack (1983), 1866 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.00 (8)

Special details

Experimental. Data for (I): [α]20°D = -32.5° (c 0.452, CH3CH2OH); 1H NMR (400 MHz, CDCl3, TMS): 0.720 (3H, d, J = 6.8 Hz, CH3), 0.766-1.142 (12H, m, CH, CH2, 3CH3), 1.221-1.388 (2H, m, 2CH), 1.611-1.660 (2H, m, CH2), 2.103-2.227 (2H, m, CH2), 2.435 (2H, d, J = 7.2 Hz, CH2), 2.495-2.515 (4H, m, 2CH2), 3.484-3.548 (1H, ddd, J = 4.4 Hz, J = 4.4 Hz,J = 4.4 Hz,CH), 3.591-3.624 (2H, m, CH2), 3.729-3.761 (2H, m, CH2), 5.751 (1H, s, CH), ESI-MS, m/z (%): Calcd for C20H34ClN2O3+([M+H]+): 385.22, Found: 385.39 (72.0).
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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)

xyzUiso*/Ueq
Cl10.92355 (9)−0.19339 (9)0.15783 (3)0.0824 (3)
C11.0114 (3)−0.1277 (3)0.25997 (11)0.0600 (7)
C20.8953 (3)−0.1150 (3)0.21895 (10)0.0527 (7)
C30.7814 (3)−0.0351 (2)0.23643 (9)0.0464 (6)
C40.8249 (3)0.0073 (3)0.29384 (9)0.0486 (6)
H40.83000.10350.29670.058*
C50.7051 (3)0.0215 (3)0.38183 (9)0.0526 (6)
H50.66990.11200.37560.063*
C60.5819 (3)−0.0524 (3)0.41368 (10)0.0604 (7)
H60.6217−0.14140.42000.072*
C70.5633 (4)0.0115 (4)0.46984 (11)0.0893 (10)
H7A0.52200.09970.46530.107*
H7B0.4903−0.03910.49110.107*
C80.7140 (4)0.0195 (4)0.50074 (12)0.1017 (12)
H8A0.69750.06480.53510.122*
H8B0.7494−0.06900.50890.122*
C90.8364 (4)0.0913 (4)0.46850 (12)0.0842 (10)
H90.80150.18200.46260.101*
C110.9897 (4)0.0966 (4)0.49839 (12)0.1230 (15)
H11A0.97750.14390.53210.185*
H11B1.06400.14070.47600.185*
H11C1.02410.00860.50600.185*
C120.4297 (3)−0.0685 (3)0.38336 (12)0.0701 (8)
H120.4543−0.10310.34700.084*
C130.3255 (4)−0.1697 (4)0.41080 (14)0.1061 (13)
H13A0.3810−0.25040.41610.159*
H13B0.2378−0.18590.38800.159*
H13C0.2921−0.13650.44550.159*
C140.3423 (4)0.0598 (4)0.37461 (14)0.0934 (11)
H14A0.25440.04360.35190.140*
H14B0.40810.12290.35710.140*
H14C0.30920.09380.40930.140*
N20.6474 (2)0.0035 (2)0.21506 (8)0.0520 (5)
C150.5990 (3)−0.0392 (3)0.16045 (10)0.0684 (8)
H15A0.6371−0.12750.15350.082*
H15B0.64250.01920.13320.082*
C160.4266 (3)−0.0384 (3)0.15570 (10)0.0656 (8)
H16A0.3968−0.06540.11920.079*
H16B0.3831−0.10050.18150.079*
N10.3681 (2)0.0924 (2)0.16674 (9)0.0557 (6)
C170.4034 (3)0.1223 (3)0.22317 (10)0.0628 (8)
H17A0.35790.05590.24660.075*
H17B0.35910.20690.23280.075*
C180.5741 (3)0.1263 (2)0.23249 (11)0.0581 (7)
H18A0.61780.19950.21230.070*
H18B0.59440.14060.27100.070*
C190.2032 (3)0.1040 (3)0.15658 (12)0.0750 (9)
H19A0.16860.18910.16980.090*
H19B0.15030.03670.17740.090*
C200.1589 (4)0.0909 (4)0.09789 (13)0.0967 (12)
H20A0.22300.14680.07600.145*
H20B0.05360.11650.09340.145*
H20C0.17150.00100.08650.145*
O30.71812 (18)−0.04391 (16)0.32993 (6)0.0511 (4)
O10.97260 (19)−0.05115 (19)0.30335 (7)0.0606 (5)
O21.1286 (2)−0.1903 (2)0.25964 (9)0.0842 (7)
C100.8549 (3)0.0261 (3)0.41285 (10)0.0655 (8)
H10A0.93000.07470.39160.079*
H10B0.8931−0.06290.41780.079*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0705 (5)0.0943 (6)0.0825 (5)0.0125 (5)0.0059 (4)−0.0335 (5)
C10.0460 (16)0.0667 (19)0.0674 (18)−0.0018 (15)0.0059 (15)−0.0001 (15)
C20.0478 (16)0.0528 (17)0.0576 (16)0.0012 (14)0.0048 (13)−0.0056 (13)
C30.0434 (14)0.0465 (16)0.0492 (14)−0.0033 (13)0.0018 (12)0.0005 (12)
C40.0420 (14)0.0505 (16)0.0532 (15)0.0018 (12)0.0031 (11)0.0020 (13)
C50.0592 (16)0.0538 (16)0.0448 (14)0.0042 (15)0.0001 (12)−0.0004 (13)
C60.0641 (18)0.0607 (17)0.0564 (16)0.0063 (16)0.0095 (14)0.0025 (14)
C70.092 (2)0.120 (3)0.0563 (18)0.002 (2)0.0142 (17)−0.0032 (19)
C80.109 (3)0.148 (4)0.0476 (17)0.007 (3)0.0026 (19)0.005 (2)
C90.091 (2)0.104 (3)0.0579 (19)0.005 (2)−0.0121 (17)−0.0102 (19)
C110.114 (3)0.186 (4)0.069 (2)−0.008 (3)−0.029 (2)−0.019 (3)
C120.0611 (19)0.076 (2)0.0736 (18)−0.0031 (18)0.0139 (16)−0.0076 (17)
C130.092 (3)0.111 (3)0.115 (3)−0.026 (2)0.037 (2)−0.002 (2)
C140.069 (2)0.111 (3)0.101 (3)0.019 (2)0.0029 (18)−0.004 (2)
N20.0535 (13)0.0548 (13)0.0477 (12)0.0074 (11)−0.0039 (9)−0.0076 (10)
C150.074 (2)0.079 (2)0.0519 (16)0.0173 (17)−0.0076 (14)−0.0158 (15)
C160.0697 (19)0.069 (2)0.0585 (16)0.0001 (17)−0.0149 (15)−0.0098 (15)
N10.0487 (13)0.0603 (15)0.0582 (13)0.0017 (11)−0.0077 (10)−0.0035 (12)
C170.0540 (17)0.070 (2)0.0643 (18)0.0115 (15)−0.0043 (14)−0.0135 (15)
C180.0570 (16)0.0541 (17)0.0631 (16)0.0097 (14)−0.0130 (14)−0.0084 (14)
C190.0573 (18)0.090 (2)0.077 (2)−0.0004 (17)−0.0157 (16)−0.0069 (18)
C200.083 (2)0.113 (3)0.094 (2)0.000 (2)−0.0368 (19)0.008 (2)
O30.0510 (10)0.0557 (11)0.0465 (9)−0.0049 (9)0.0040 (8)−0.0008 (8)
O10.0435 (10)0.0781 (13)0.0601 (11)0.0085 (10)−0.0047 (8)−0.0019 (10)
O20.0541 (12)0.0954 (16)0.1032 (17)0.0258 (12)−0.0054 (11)−0.0103 (14)
C100.0653 (18)0.079 (2)0.0524 (16)−0.0018 (17)−0.0031 (13)0.0017 (15)

Geometric parameters (Å, °)

Cl1—C21.712 (2)C12—H120.9800
C1—O21.203 (3)C13—H13A0.9600
C1—O11.358 (3)C13—H13B0.9600
C1—C21.431 (4)C13—H13C0.9600
C2—C31.351 (3)C14—H14A0.9600
C3—N21.338 (3)C14—H14B0.9600
C3—C41.518 (3)C14—H14C0.9600
C4—O31.384 (3)N2—C181.463 (3)
C4—O11.437 (3)N2—C151.468 (3)
C4—H40.9800C15—C161.507 (4)
C5—O31.438 (3)C15—H15A0.9700
C5—C101.511 (3)C15—H15B0.9700
C5—C61.524 (4)C16—N11.447 (3)
C5—H50.9800C16—H16A0.9700
C6—C71.529 (4)C16—H16B0.9700
C6—C121.529 (4)N1—C171.447 (3)
C6—H60.9800N1—C191.463 (3)
C7—C81.518 (4)C17—C181.506 (3)
C7—H7A0.9700C17—H17A0.9700
C7—H7B0.9700C17—H17B0.9700
C8—C91.514 (5)C18—H18A0.9700
C8—H8A0.9700C18—H18B0.9700
C8—H8B0.9700C19—C201.494 (4)
C9—C101.523 (4)C19—H19A0.9700
C9—C111.524 (4)C19—H19B0.9700
C9—H90.9800C20—H20A0.9600
C11—H11A0.9600C20—H20B0.9600
C11—H11B0.9600C20—H20C0.9600
C11—H11C0.9600C10—H10A0.9700
C12—C141.524 (4)C10—H10B0.9700
C12—C131.527 (4)
O2—C1—O1121.2 (3)C12—C13—H13C109.5
O2—C1—C2130.0 (3)H13A—C13—H13C109.5
O1—C1—C2108.7 (2)H13B—C13—H13C109.5
C3—C2—C1110.6 (2)C12—C14—H14A109.5
C3—C2—Cl1131.4 (2)C12—C14—H14B109.5
C1—C2—Cl1118.0 (2)H14A—C14—H14B109.5
N2—C3—C2133.9 (2)C12—C14—H14C109.5
N2—C3—C4119.8 (2)H14A—C14—H14C109.5
C2—C3—C4106.2 (2)H14B—C14—H14C109.5
O3—C4—O1110.14 (19)C3—N2—C18121.1 (2)
O3—C4—C3108.46 (19)C3—N2—C15121.4 (2)
O1—C4—C3104.89 (19)C18—N2—C15113.0 (2)
O3—C4—H4111.1N2—C15—C16110.8 (2)
O1—C4—H4111.1N2—C15—H15A109.5
C3—C4—H4111.1C16—C15—H15A109.5
O3—C5—C10113.0 (2)N2—C15—H15B109.5
O3—C5—C6106.3 (2)C16—C15—H15B109.5
C10—C5—C6111.5 (2)H15A—C15—H15B108.1
O3—C5—H5108.6N1—C16—C15110.0 (2)
C10—C5—H5108.6N1—C16—H16A109.7
C6—C5—H5108.6C15—C16—H16A109.7
C5—C6—C7109.0 (2)N1—C16—H16B109.7
C5—C6—C12114.6 (2)C15—C16—H16B109.7
C7—C6—C12112.9 (2)H16A—C16—H16B108.2
C5—C6—H6106.6C17—N1—C16107.2 (2)
C7—C6—H6106.6C17—N1—C19110.7 (2)
C12—C6—H6106.6C16—N1—C19112.9 (2)
C8—C7—C6112.2 (3)N1—C17—C18111.1 (2)
C8—C7—H7A109.2N1—C17—H17A109.4
C6—C7—H7A109.2C18—C17—H17A109.4
C8—C7—H7B109.2N1—C17—H17B109.4
C6—C7—H7B109.2C18—C17—H17B109.4
H7A—C7—H7B107.9H17A—C17—H17B108.0
C9—C8—C7112.1 (3)N2—C18—C17111.4 (2)
C9—C8—H8A109.2N2—C18—H18A109.4
C7—C8—H8A109.2C17—C18—H18A109.4
C9—C8—H8B109.2N2—C18—H18B109.4
C7—C8—H8B109.2C17—C18—H18B109.4
H8A—C8—H8B107.9H18A—C18—H18B108.0
C8—C9—C10109.4 (3)N1—C19—C20114.2 (3)
C8—C9—C11112.6 (3)N1—C19—H19A108.7
C10—C9—C11110.6 (3)C20—C19—H19A108.7
C8—C9—H9108.0N1—C19—H19B108.7
C10—C9—H9108.0C20—C19—H19B108.7
C11—C9—H9108.0H19A—C19—H19B107.6
C9—C11—H11A109.5C19—C20—H20A109.5
C9—C11—H11B109.5C19—C20—H20B109.5
H11A—C11—H11B109.5H20A—C20—H20B109.5
C9—C11—H11C109.5C19—C20—H20C109.5
H11A—C11—H11C109.5H20A—C20—H20C109.5
H11B—C11—H11C109.5H20B—C20—H20C109.5
C14—C12—C13109.8 (3)C4—O3—C5116.3 (2)
C14—C12—C6114.3 (3)C1—O1—C4109.41 (19)
C13—C12—C6112.0 (3)C5—C10—C9111.8 (2)
C14—C12—H12106.8C5—C10—H10A109.3
C13—C12—H12106.8C9—C10—H10A109.3
C6—C12—H12106.8C5—C10—H10B109.3
C12—C13—H13A109.5C9—C10—H10B109.3
C12—C13—H13B109.5H10A—C10—H10B107.9
H13A—C13—H13B109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C4—H4···O2i0.982.533.361 (4)142

Symmetry codes: (i) −x+2, y+1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: XU2787).

References

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