(Z)-Isobutyl 2-benzamido-3-(4-chloro­phen­yl)acrylate

Gui-Fa Su; Zhong-Chang Wang; Wan-Yun Huang; Zhi-Xin Wang; Zi-Lu Chen

doi:10.1107/S1600536809043931

. 2009 Oct 28;65(Pt 11):o2890. doi: 10.1107/S1600536809043931

(Z)-Isobutyl 2-benzamido-3-(4-chlorophenyl)acrylate

Gui-Fa Su ^a,^*, Zhong-Chang Wang ^a, Wan-Yun Huang ^a, Zhi-Xin Wang ^a, Zi-Lu Chen ^a

PMCID: PMC2970985 PMID: 21578473

Abstract

The title compound, C₂₀H₂₀ClNO₃, is a α-amino acid derivative which displays a Z configuration about the C=C double bond. The dihedral angle betwen the aromatic rings is 87.75 (12)°. The molecular conformation is stabilized by an intramolecular C—H⋯N hydrogen bond. In the crystal structure, centrosymmetrically related molecules interact through intermolecular C—H⋯O hydrogen-bond interactions, forming dimers. The dimers are further linked into chains parallel to the a axis by N—H⋯O hydrogen bonds. The methyl groups of the isopropyl group are disordered over two positions with occupancy factors of 0.5.

Related literature

For the synthesis and crystal structure of related compounds, see: Jiménez et al. (2000 ▶); Peggion et al. (2003 ▶).

Experimental

Crystal data

C₂₀H₂₀ClNO₃
M _r = 357.82
Triclinic,
a = 5.0179 (10) Å
b = 12.581 (2) Å
c = 16.293 (3) Å
α = 67.623 (11)°
β = 83.991 (15)°
γ = 79.548 (14)°
V = 934.6 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 293 K
0.50 × 0.40 × 0.25 mm

Data collection

Rigaku AFC-7S Mercury diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998 ▶) T _min = 0.897, T _max = 0.946
9082 measured reflections
3380 independent reflections
2224 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.073
wR(F ²) = 0.213
S = 1.10
3380 reflections
231 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2000 ▶); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809043931/rz2372sup1.cif

e-65-o2890-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809043931/rz2372Isup2.hkl

e-65-o2890-Isup2.hkl^{(165.7KB, 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
C3—H3⋯O1ⁱ	0.93	2.43	3.299 (4)	155
N1—H1⋯O3ⁱⁱ	0.86	2.07	2.916 (3)	169
C9—H9⋯N1	0.93	2.55	3.103 (4)	119

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

Acknowledgments

The authors thank the Natural Science Foundation of Guangxi Zhuang Autonomous Region (grant No. 0731054)

supplementary crystallographic information

Comment

As part of a study on the effect of the conformationally restricted molecular substitution on the crystal structures of biologically important class of compounds, we report herein the crystal structure of the title compound. Small and medium α-amino acids are generally highly flexible molecules that exist in solution in a dynamic equilibrium of interchanging conformations. As a consequence, most natural α-amino acids with physiological activity cannot be used for therapeutic purposes so we developed the introduction of conformational constrains. In comparison with native α-amino acids, side chain restricted analogues usually display more favorable pharmacological properties (Jiménez et al., 2000; Peggion et al., 2003).

The molecule of the title compound (Fig. 1) displays a Z configuration about the C2C3 double bond. The molecular conformation is enforced by an intramolecular C—H···N hydrogen bond (Table 1). The C19 and C20 methyl groups of the isopropyl group are disordered over two positions with occupancy factors of 0.5. The dihedral angle formed by the aromatic rings is 87.75 (12)°. In the crystal packing, centrosymmetrically related molecules are linked into dimers by intermolecular C—H···O hydrogen bonds. The dimers are further connected by N—H···O hydrogen bonds to form chains parallel to the a axis (Fig. 2).

Experimental

Compound B (Fig. 3): to a 100 ml round-bottomed flask was added 1.4 g (1.18 ml, 0.01 mol) of redistilled 4-chlorobenzaldehyde, 1.79 g (0.01 mol) of benzoylglycine, 3.1 g (2.8 ml, 0.03 mol) of acetic anhydride and 0.82 g (0.01 mol) of anhydrous sodium acetate, and the mixture was heated on an electric hotplace with constant shaking. Once liquefied completely, the round-bottomed flask was transferred to a water bath and heated at 100 °C for 2 h, then 16 ml of ethanol was added slowly to the flask and the mixture allowed to stand overnight. The crystalline product was filtered with suction, washed twice with 25 ml of ice-cold alcohol and twice with 25 ml of boiling water and dried to afford 1.91 g of pure compound B (yield 64%).

Compound C (Fig. 3): to a 0.1% solution of sodium methoxide in absolute methanol (40 ml) was added 2.1 g of compound B (3.52 mmol). The mixture was heated to 75 °C under vigorously stirring until TLC analysis indicated that the starting material had disappeared (about 2 h). The product was collected by vacuum filtration and washed with small portions of cold methanol to afford 2.16 g of compound C as a white solid (yield 92%).

Title compound (D, Fig. 3): to a 100 ml round-bottomed flask was added 0.303 g (1.0 mmol) of compound C, 9.9 g (10 ml, 0.13 mol) of redistilled isobutanol, 10 ml of redistilled cyclohexane and 2 ml of concentrated sulfuric acid under stirring. The mixture was refluxed 4 h with stirring, then cooled and the product extracted with chloroform (2× 15 ml). The combined organic layer was dried over MgSO₄, filtered and the solvent removed under reduced pressure to afford 0.293 g of the title compound as a white solid (yield 81%). Crystals suitable for X-ray analysis were obtained by slow evaporation of a dichloromethane-ethanol solution (1:2 v/v). IR 3837, 3745, 3648, 3165, 1737. ¹H NMR (DMSO-d₆, 500 MHz) δ 0.85 (d, 6H, J=6.75 Hz); 1.86 (m, 1H); 3.91 (d, 2H, J=6.4 Hz); 7.38 (s, 1H); 7.46 (d, 2H, J=8.5 Hz); 7.49–7.53 (m, 2H); 7.57–7.59 (m, 1H); 7.68 (d, 2H, J=8.5 Hz); 7.93 (d, 2H, J=7.1 Hz); 10.0 (s, 1H). ¹³C NMR (DMSO-d₆, 125.8 MHz) δ 18.7, 27.2, 70.7, 127.4, 127.5, 128.4, 128.6, 131.3, 131.6, 131.8, 132.3, 133.2, 133.9, 164.8, 166.4.