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

Zhao-yang Li; Xiu-mei Song; Zhao-yang Wang; Kai Yang

doi:10.1107/S1600536809012720

. 2009 Apr 10;65(Pt 5):o1030. doi: 10.1107/S1600536809012720

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

Zhao-yang Li ^a, Xiu-mei Song ^a, Zhao-yang Wang ^a,^*, Kai Yang ^a

PMCID: PMC2977713 PMID: 21583849

Abstract

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.

Related literature

For chiral 5-(l-menthyloxy)furan-2(5H)-ones 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-aminofuran-2(5H)-one 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 (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one, see: Chen & Geng (1993 ▶).

Experimental

Crystal data

C₁₇H₂₆ClNO₅
M _r = 359.84
Orthorhombic,
a = 11.2481 (15) Å
b = 19.642 (2) Å
c = 9.0668 (11) Å
V = 2003.1 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.30 × 0.23 × 0.18 mm

Data collection

Bruker APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.761, T _max = 0.846 (expected range = 0.866–0.962)
10244 measured reflections
3534 independent reflections
2879 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.120
S = 1.08
3534 reflections
222 parameters
312 restraints
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.34 e Å⁻³
Absolute structure: Flack (1983 ▶), 1499 Friedel pairs
Flack parameter: 0.00 (10)

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809012720/bq2134sup1.cif

e-65-o1030-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809012720/bq2134Isup2.hkl

e-65-o1030-Isup2.hkl^{(173.3KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O5ⁱ	0.86	2.20	2.975 (4)	150
O4—H4⋯O3ⁱⁱ	0.82	1.86	2.655 (3)	164

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Symmetry codes: (i) Inline graphic ; (ii) .

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

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).

Experimental

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).