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Acta Cryst. (2009). E65, o1030    [ doi:10.1107/S1600536809012720 ]

N-[(2S)-4-Chloro-2-(L-menthyloxy)-5-oxo-2,5-dihydro-3-furyl]-L-alanine

Z. Li, X. Song, Z. Wang and K. Yang

Abstract top

The title compound, C17H26ClNO5, was prepared via a tandem asymmetric Michael addition-elimination reaction of (5S)-3,4-dichloro-5-(L-menthyloxy)furan-2(5H)-one and L-alanine in the presence of potassium hydroxide. The five-membered furanone ring is approximately planar while the six-membered menthyloxy ring adopts a chair conformation. The crystal packing is stabilized by intermolecular O-H...O and N-H...O hydrogen bonds.

Comment top

Chiral 5-(l-menthyloxy)-2(5H)-furanones have been extensively utilized as key building blocks in the synthesis of supramolecules and important natural products since 1980's (Feringa et al., 1988; Lattmann et al., 1999), especially in asymmetric synthesis (He et al., 2006). 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). Herein we report the crystal structure of the title compound N-[3-chloro-5-(S)-(l-menthyloxy)-2(5H)-4-furanon-yl]-L-alanine, namely C17H26ClNO5, obtained via tandem asymmetric Michael addition-elimination reaction, with chiral building blocks 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone and L-alanine.

The structure of the title compound (I) is illustrated in Fig. 1. The asymmetric unit of the title compound contains two independent rings: a five-membered furanone ring and a six-membered menthyloxy ring connected each other via C1—O1—C11 ether bond, having five chiral centers (C1(R), C2(S), C5(R), C11(S), C15(S)). The furanone ring of O2—C14—C13—C12—C11 is approximately planar, whereas the cyclohexane ring displays a chair conformation with three substituents occupying equatorial positions. In addition, the molecules of (I) are linked by O4—H4···O3 and N1—H1A···O5 intermolecular hydrogen bonds, giving rise to three-dimensional structure (Tab. 1 and Fig. 2). The bond distances and angles are mostly in agreement with the expected values (Wang et al., 2008).

Related literature top

For chiral 5-(L-menthyloxy)-2(5H)-furanones as key building blocks in the synthesis of supramolecules and important natural products, see: Feringa & De Jong (1988); He et al. (2006); Lattmann et al. (1999). For the use of 4-amino-2(5H)-furanone in chemical,pharmaceutical and agrochemical research, see: Kimura et al. (2000); Tanoury et al. (2008). For a related structure, see: Wang et al. (2008). For the synthesis of the chiral synthon 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone, see: Chen & Geng (1993).

Experimental top

The chiral synthon 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone was prepared according to the literature procedure (Chen et al., 1993). After the mixture of L-alanine (0.18 g, 2.03 mmol) and potassium hydroxide (0.1274 g, 2.28 mmol) was dissolved in absolute ethyl alcohol under a nitrogen atmosphere, dichloromethane solution of 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone (0.7494 g, 2.50 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, and the pH of the solution was adjusted to 3–4 with 15% of HCl aqueous solution. 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) 0.4348 g (59.5%). 1H NMR δ (400 MHz, CDCl3, TMS): 0.825–0.850 (3H, m, CH3-7), 0.901–0.955 (7H, m, CH-8, CH3-9, 10), 0.994–1.154 (2H, m, CH2-4), 1.340–1.439 (2H,m, CH-5, CH-2), 1.581–1.607 (3H, m, CH3-16), 1.630–1.700 (2H, m, CH2-3), 2.065–2.233 (2H, m, CH2-6), 3.520–3.602 (1H, m, CH-1), 4.771–4.864 (1H, m, CH-15), 5.195 (1H, s, NH), 5.704 (1H, s, CH-11), 8.950 (1H, s, COO-H); [α]20°D = 53.96° (c 0.467, CH3CH2OH); ESI-MS, m/z (%): Calcd for C17H27ClNO5+ ([M+H]+): 360.16, Found: 360.32 (95.0).

Refinement top

All H atoms were positioned in calculated positions (O—H = 0.82Å; N—H = 0.86Å; C—H =0.96Å or 0.97Å or 0.98Å) and were refined using a riding model, with Uiso(H) = 1.2 Ueq(C) for methylene H atoms and Uiso(H) = 1.5 Ueq(O) for methyl or hydroxyl H atoms Uiso(H) = 1.2 Ueq(N) for amino H atoms.

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Displacement ellipsoid plot (40% probability level) of the title compound (I), with atom numbering of structurally unique non-H atoms and the H atoms.
[Figure 2] Fig. 2. The packing diagram of the title compound (I) (viewed down the c axis).
N-[(2S)-4-Chloro-2-(L-menthyloxy)-5-oxo- 2,5-dihydro-3-furyl]-L-alanine top
Crystal data top
C17H26ClNO5F(000) = 768.0
Mr = 359.84Dx = 1.193 Mg m−3
Orthorhombic, P21212Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2 2abCell parameters from 2460 reflections
a = 11.2481 (15) Åθ = 2.3–20.5°
b = 19.642 (2) ŵ = 0.21 mm−1
c = 9.0668 (11) ÅT = 293 K
V = 2003.1 (4) Å3Block, colorless
Z = 40.30 × 0.23 × 0.18 mm
Data collection top
Bruker APEXII area-detector
diffractometer		3534 independent reflections
Radiation source: fine-focus sealed tube2879 reflections with I > 2σ(I)
graphiteRint = 0.037
ω scanθmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		h = −13→11
Tmin = 0.761, Tmax = 0.846k = −23→22
10244 measured reflectionsl = −10→7
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)] = 0.046H-atom parameters constrained
wR(F2) = 0.120 w = 1/[σ2(Fo2) + (0.0567P)2 + 0.3483P]
where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max < 0.001
3534 reflectionsΔρmax = 0.33 e Å−3
222 parametersΔρmin = −0.34 e Å−3
312 restraintsAbsolute structure: Flack (1983), 1499 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.00 (10)
Crystal data top
C17H26ClNO5V = 2003.1 (4) Å3
Mr = 359.84Z = 4
Orthorhombic, P21212Mo Kα radiation
a = 11.2481 (15) ŵ = 0.21 mm−1
b = 19.642 (2) ÅT = 293 K
c = 9.0668 (11) Å0.30 × 0.23 × 0.18 mm
Data collection top
Bruker APEXII area-detector
diffractometer		3534 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		2879 reflections with I > 2σ(I)
Tmin = 0.761, Tmax = 0.846Rint = 0.037
10244 measured reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.120Δρmax = 0.33 e Å−3
S = 1.08Δρmin = −0.34 e Å−3
3534 reflectionsAbsolute structure: Flack (1983), 1499 Friedel pairs
222 parametersFlack parameter: 0.00 (10)
312 restraints
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
C10.4798 (4)0.78198 (19)0.8644 (4)0.0536 (9)
H10.55450.79920.82320.064*
C20.4754 (4)0.79762 (19)1.0295 (4)0.0619 (10)
H20.39960.77971.06610.074*
C30.5733 (5)0.7571 (2)1.1058 (6)0.0907 (13)
H3A0.64990.77421.07350.109*
H3B0.56770.76451.21140.109*
C40.5674 (6)0.6817 (2)1.0753 (6)0.0968 (14)
H4A0.63450.65941.12190.116*
H4B0.49530.66331.11850.116*
C50.5686 (6)0.6664 (2)0.9133 (6)0.0897 (13)
H50.64550.68070.87290.108*
C60.4707 (4)0.70649 (18)0.8358 (4)0.0651 (10)
H6A0.47560.69830.73050.078*
H6B0.39400.69030.86960.078*
C70.5537 (6)0.5895 (2)0.8864 (7)0.1183 (17)
H7A0.61220.56500.94230.177*
H7B0.56400.57990.78330.177*
H7C0.47560.57560.91670.177*
C80.4770 (5)0.8738 (2)1.0660 (5)0.0761 (12)
H80.41680.89551.00380.091*
C90.4415 (6)0.8870 (3)1.2264 (6)0.1027 (15)
H9A0.37490.85871.25170.154*
H9B0.42000.93401.23810.154*
H9C0.50720.87651.29000.154*
C100.5941 (6)0.9084 (3)1.0329 (7)0.1110 (16)
H10A0.65460.89041.09670.166*
H10B0.58640.95651.04910.166*
H10C0.61560.90010.93210.166*
C110.3749 (3)0.81985 (15)0.6456 (3)0.0374 (7)
H110.45340.82770.60180.045*
C120.2880 (3)0.87618 (15)0.6067 (3)0.0347 (7)
C130.1874 (3)0.84593 (15)0.5583 (4)0.0383 (7)
C140.2086 (3)0.77365 (15)0.5426 (4)0.0393 (7)
C150.2405 (3)0.99911 (15)0.6191 (4)0.0427 (8)
H150.18630.99200.53590.051*
C160.1683 (3)1.00945 (19)0.7577 (5)0.0611 (10)
H16A0.11880.97040.77410.092*
H16B0.11931.04920.74690.092*
H16C0.22081.01540.84020.092*
C170.3137 (3)1.06179 (15)0.5905 (4)0.0428 (8)
Cl10.04908 (8)0.87823 (4)0.51989 (12)0.0612 (3)
N10.3197 (2)0.94048 (12)0.6313 (3)0.0440 (7)
H1A0.39220.94810.65630.053*
O10.3799 (2)0.81852 (11)0.7981 (2)0.0423 (5)
O20.31972 (19)0.75881 (10)0.5881 (3)0.0426 (6)
O30.1433 (2)0.72965 (11)0.4945 (3)0.0532 (6)
O40.2496 (2)1.10975 (12)0.5305 (4)0.0780 (10)
H40.29191.14270.51220.117*
O50.4163 (2)1.06720 (11)0.6217 (3)0.0610 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.061 (2)0.0474 (17)0.0526 (19)0.0069 (16)−0.0111 (16)0.0100 (15)
C20.080 (2)0.0552 (19)0.051 (2)−0.0053 (18)−0.0131 (18)0.0075 (17)
C30.120 (3)0.078 (2)0.074 (2)0.009 (2)−0.036 (2)0.007 (2)
C40.135 (3)0.074 (3)0.081 (3)0.019 (3)−0.034 (3)0.021 (2)
C50.127 (3)0.065 (2)0.077 (3)0.031 (2)−0.025 (3)0.016 (2)
C60.094 (3)0.0458 (19)0.056 (2)0.0143 (19)−0.0131 (19)0.0062 (16)
C70.181 (4)0.075 (3)0.099 (3)0.046 (3)−0.034 (3)0.014 (3)
C80.102 (3)0.064 (2)0.062 (2)−0.001 (2)−0.015 (2)−0.005 (2)
C90.141 (4)0.094 (3)0.073 (3)−0.006 (3)−0.003 (3)−0.020 (3)
C100.137 (4)0.090 (3)0.107 (3)−0.031 (3)−0.005 (3)−0.008 (3)
C110.0426 (16)0.0299 (15)0.0397 (18)−0.0006 (14)−0.0029 (14)0.0015 (13)
C120.0369 (15)0.0272 (14)0.0401 (17)−0.0002 (13)0.0019 (13)0.0026 (13)
C130.0395 (16)0.0291 (14)0.0463 (19)0.0002 (13)−0.0049 (14)−0.0001 (14)
C140.0437 (18)0.0324 (16)0.0418 (19)−0.0012 (14)−0.0017 (14)−0.0025 (14)
C150.0397 (16)0.0267 (15)0.061 (2)0.0010 (13)−0.0075 (15)0.0044 (15)
C160.053 (2)0.048 (2)0.083 (3)−0.0019 (17)0.0107 (18)0.0009 (19)
C170.0399 (19)0.0279 (15)0.061 (2)0.0008 (14)−0.0058 (16)0.0032 (15)
Cl10.0444 (5)0.0433 (5)0.0960 (8)0.0070 (4)−0.0225 (5)−0.0125 (5)
N10.0358 (15)0.0283 (14)0.068 (2)−0.0006 (12)−0.0108 (14)0.0035 (13)
O10.0457 (13)0.0385 (12)0.0426 (14)0.0057 (10)−0.0046 (10)0.0046 (10)
O20.0428 (13)0.0264 (11)0.0585 (15)0.0032 (10)−0.0074 (10)−0.0051 (10)
O30.0541 (14)0.0321 (12)0.0734 (17)−0.0052 (11)−0.0091 (13)−0.0130 (12)
O40.0509 (15)0.0357 (14)0.147 (3)−0.0056 (12)−0.0219 (17)0.0330 (18)
O50.0410 (15)0.0330 (12)0.109 (2)−0.0023 (10)−0.0109 (14)0.0093 (14)
Geometric parameters (Å, °) top
C1—O11.462 (4)C9—H9C0.9600
C1—C61.509 (5)C10—H10A0.9600
C1—C21.529 (6)C10—H10B0.9600
C1—H10.9800C10—H10C0.9600
C2—C31.524 (6)C11—O11.384 (4)
C2—C81.532 (6)C11—O21.447 (4)
C2—H20.9800C11—C121.518 (4)
C3—C41.509 (6)C11—H110.9800
C3—H3A0.9700C12—N11.331 (4)
C3—H3B0.9700C12—C131.351 (4)
C4—C51.499 (8)C13—C141.447 (4)
C4—H4A0.9700C13—Cl11.716 (3)
C4—H4B0.9700C14—O31.215 (4)
C5—C61.525 (6)C14—O21.348 (4)
C5—C71.540 (7)C15—N11.460 (4)
C5—H50.9800C15—C171.504 (4)
C6—H6A0.9700C15—C161.510 (5)
C6—H6B0.9700C15—H150.9800
C7—H7A0.9600C16—H16A0.9600
C7—H7B0.9600C16—H16B0.9600
C7—H7C0.9600C16—H16C0.9600
C8—C101.512 (7)C17—O51.193 (4)
C8—C91.530 (7)C17—O41.305 (4)
C8—H80.9800N1—H1A0.8600
C9—H9A0.9600O4—H40.8200
C9—H9B0.9600
O1—C1—C6111.1 (3)C8—C9—H9A109.5
O1—C1—C2106.2 (3)C8—C9—H9B109.5
C6—C1—C2111.3 (3)H9A—C9—H9B109.5
O1—C1—H1109.4C8—C9—H9C109.5
C6—C1—H1109.4H9A—C9—H9C109.5
C2—C1—H1109.4H9B—C9—H9C109.5
C3—C2—C1108.5 (4)C8—C10—H10A109.5
C3—C2—C8113.8 (4)C8—C10—H10B109.5
C1—C2—C8114.0 (3)H10A—C10—H10B109.5
C3—C2—H2106.7C8—C10—H10C109.5
C1—C2—H2106.7H10A—C10—H10C109.5
C8—C2—H2106.7H10B—C10—H10C109.5
C4—C3—C2113.4 (4)O1—C11—O2111.2 (2)
C4—C3—H3A108.9O1—C11—C12105.8 (2)
C2—C3—H3A108.9O2—C11—C12104.1 (2)
C4—C3—H3B108.9O1—C11—H11111.8
C2—C3—H3B108.9O2—C11—H11111.8
H3A—C3—H3B107.7C12—C11—H11111.8
C5—C4—C3112.1 (4)N1—C12—C13134.1 (3)
C5—C4—H4A109.2N1—C12—C11118.7 (3)
C3—C4—H4A109.2C13—C12—C11107.1 (3)
C5—C4—H4B109.2C12—C13—C14109.0 (3)
C3—C4—H4B109.2C12—C13—Cl1131.5 (2)
H4A—C4—H4B107.9C14—C13—Cl1119.5 (2)
C4—C5—C6109.9 (4)O3—C14—O2121.1 (3)
C4—C5—C7110.5 (4)O3—C14—C13129.3 (3)
C6—C5—C7110.8 (5)O2—C14—C13109.6 (3)
C4—C5—H5108.5N1—C15—C17109.0 (2)
C6—C5—H5108.5N1—C15—C16111.8 (3)
C7—C5—H5108.5C17—C15—C16109.1 (3)
C1—C6—C5112.3 (4)N1—C15—H15109.0
C1—C6—H6A109.1C17—C15—H15109.0
C5—C6—H6A109.1C16—C15—H15109.0
C1—C6—H6B109.1C15—C16—H16A109.5
C5—C6—H6B109.1C15—C16—H16B109.5
H6A—C6—H6B107.9H16A—C16—H16B109.5
C5—C7—H7A109.5C15—C16—H16C109.5
C5—C7—H7B109.5H16A—C16—H16C109.5
H7A—C7—H7B109.5H16B—C16—H16C109.5
C5—C7—H7C109.5O5—C17—O4124.7 (3)
H7A—C7—H7C109.5O5—C17—C15124.2 (3)
H7B—C7—H7C109.5O4—C17—C15111.1 (3)
C10—C8—C9109.9 (4)C12—N1—C15124.9 (3)
C10—C8—C2114.0 (4)C12—N1—H1A117.5
C9—C8—C2111.6 (4)C15—N1—H1A117.5
C10—C8—H8107.0C11—O1—C1116.8 (3)
C9—C8—H8107.0C14—O2—C11109.2 (2)
C2—C8—H8107.0C17—O4—H4109.5
O1—C1—C2—C3176.5 (3)N1—C12—C13—Cl1−5.9 (6)
C6—C1—C2—C355.4 (5)C11—C12—C13—Cl1170.3 (3)
O1—C1—C2—C8−55.6 (5)C12—C13—C14—O3−175.4 (3)
C6—C1—C2—C8−176.7 (4)Cl1—C13—C14—O35.8 (5)
C1—C2—C3—C4−54.8 (6)C12—C13—C14—O23.1 (4)
C8—C2—C3—C4177.1 (4)Cl1—C13—C14—O2−175.7 (2)
C2—C3—C4—C555.4 (7)N1—C15—C17—O5−23.0 (5)
C3—C4—C5—C6−53.4 (7)C16—C15—C17—O599.4 (4)
C3—C4—C5—C7−176.0 (5)N1—C15—C17—O4158.5 (3)
O1—C1—C6—C5−175.7 (4)C16—C15—C17—O4−79.2 (4)
C2—C1—C6—C5−57.5 (5)C13—C12—N1—C154.8 (6)
C4—C5—C6—C155.4 (6)C11—C12—N1—C15−171.0 (3)
C7—C5—C6—C1177.8 (5)C17—C15—N1—C12−156.0 (3)
C3—C2—C8—C1056.0 (6)C16—C15—N1—C1283.2 (4)
C1—C2—C8—C10−69.1 (5)O2—C11—O1—C183.7 (3)
C3—C2—C8—C9−69.2 (6)C12—C11—O1—C1−163.9 (3)
C1—C2—C8—C9165.7 (4)C6—C1—O1—C11−67.5 (4)
O1—C11—C12—N169.8 (3)C2—C1—O1—C11171.3 (3)
O2—C11—C12—N1−172.9 (3)O3—C14—O2—C11−177.5 (3)
O1—C11—C12—C13−107.0 (3)C13—C14—O2—C113.8 (3)
O2—C11—C12—C1310.2 (3)O1—C11—O2—C14105.0 (3)
N1—C12—C13—C14175.6 (3)C12—C11—O2—C14−8.4 (3)
C11—C12—C13—C14−8.2 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O5i0.862.202.975 (4)150
O4—H4···O3ii0.821.862.655 (3)164
Symmetry codes: (i) −x+1, −y+2, z; (ii) −x+1/2, y+1/2, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O5i0.862.202.975 (4)150
O4—H4···O3ii0.821.862.655 (3)164
Symmetry codes: (i) −x+1, −y+2, z; (ii) −x+1/2, y+1/2, −z+1.
Acknowledgements top

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).

references
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