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

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.

The title compound, C 20 H 20 ClNO 3 , is a -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-HÁ Á ÁN hydrogen bond. In the crystal structure, centrosymmetrically related molecules interact through intermolecular C-HÁ Á ÁO hydrogen-bond interactions, forming dimers. The dimers are further linked into chains parallel to the a axis by N-HÁ Á ÁO hydrogen bonds. The methyl groups of the isopropyl group are disordered over two positions with occupancy factors of 0.5.   Table 1 Hydrogen-bond geometry (Å , ). supporting information . E65, o2890 [https://doi.org/10.1107/S1600536809043931] (Z)-Isobutyl 2-benzamido-3-(4-chlorophenyl)acrylate Gui-Fa Su, Zhong-Chang Wang, Wan-Yun Huang, Zhi-Xin Wang and Zi-Lu Chen S1. Comment

Experimental
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 αamino 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).

S2. 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).

S3. Refinement
The H atom on C18 was located in a difference Fourier map and refined isotropically. Other H atom were positioned geometrically and included in the refinement in the riding-model approximation, with C-H = 0.93-0.97 Å, N-H = 0.86 Å, and with Uĩso~(H) = 1.5U~eq~(C, N). The methyl groups C19 and C20 of the isopropyl group are disordered over two positions with occupancy factors of 0.5 and were refined isotropically. The C-C distances within the isopropyl group were restrained to be 1.54 (1) Å.

Figure 1
The molecular structure of the title compound, showing 20% probability displacement ellipsoids.   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2 )
x y z U iso */U eq Occ. (