Methyl (Z)-2-chloro-3-(2-methoxycarbonylphenyl)prop-2-enoate

In the title compound, C12H11ClO4, the propenoate C=C bond is in the Z configuration. The propenoate C=O and C=C groups are essentially coplanar [C=C—C=O torsion angle = 172.4 (3)°] with the O atom synperiplanar to the Cl atom. However, the π systems of the aromatic ring and chloropropenoate substituent are not coplanar; the corresponding dihedral angle is 51.5 (1)°. The noncoplanarity is likely due to steric interactions between the propenoate H atom and the ortho-methoxycarbonyl group on the aromatic ring. Even in the observed noncoplanar conformation, the ortho C=O to H distance (2.40 Å) is less than the sum of the van der Waals radii of O and H (2.65 Å).

In the title compound, C 12 H 11 ClO 4 , the propenoate C C bond is in the Z configuration. The propenoate C O and C C groups are essentially coplanar [C C-C O torsion angle = 172.4 (3) ] with the O atom synperiplanar to the Cl atom. However, the systems of the aromatic ring and chloropropenoate substituent are not coplanar; the corresponding dihedral angle is 51.5 (1) . The noncoplanarity is likely due to steric interactions between the propenoate H atom and the ortho-methoxycarbonyl group on the aromatic ring. Even in the observed noncoplanar conformation, the ortho C O to H distance (2.40 Å ) is less than the sum of the van der Waals radii of O and H (2.65 Å ).

Comment
The title compound (1) is of interest in the development of anticancer enzyme inhibitors. Determination of the E/Z stereochemistry and the preferred conformation were needed for in silico docking of 1 and its derivatives to target enzymes.
Synthesis of 1 was carried out as shown in Fig. 1. Esterification of o-carboxycinnamic acid was accomplished by treatment with CH 3 OH/HCl. The subsequent formation of the Z-isomer during synthesis can be rationalized on the basis of the known lack of stereospecificity of the dichlorination reaction when applied to aromatic-substituted alkenes, carried out essentially by the method of Markó et al. (1997).
Subsequent elimination of HCl from the dichloro derivative by treatment with triethylamine in dichloromethane produced 1 in ~10:1 ratio (by NMR) with its E isomer. Regioselectivity (i.e., preferential formation of the 2-chloropropenoate over 3-chloropropenoate) results from the more facile deprotonation of the more acidic H atom in the α-position to the ester carbonyl group, with loss of the 3-chlorine atom. Fig. 2 shows that 1 has Z configuration at the alkene double bond and that the π systems of the aromatic ring and the chloropropenoate substituent are not coplanar. The C2-C1-C7-C8 torsion angle is 133.5 (3)° and the C6-C1-C7-C8 torsion angle is -49.4 (4)°; the dihedral angle formed by the plane of the aromatic ring and the plane of the chloropropenoate substituent (C7, C8, C9, Cl1, O1, O2) is equal to 51.5 (1)°. The ortho-methoxycarbonyl substituent is slightly non-coplanar with the aromatic ring, as shown by the O3-C11-C2-C1 torsion angle of -10.7 (4)°. Loss of resonance stabilization by twisting of the ortho-methoxycarbonyl and propenoate groups relative to the aromatic ring is presumably balanced by relief of steric strain due to proximity of the ortho-carbonyl oxygen and the propenoate hydrogen.
Acetyl chloride (1 ml) was slowly added to 25 ml of cold methanol in a 100-ml round-bottom flask. The reaction mixture was warmed slowly then refluxed for 10 minutes prior to addition of 381 mg (2 mmol) of 2-CCA. The reaction mixture was refluxed and monitored by thin-layer chromatography (TLC). Typically, the reaction was complete in less than 2 h. The reaction mixture was concentrated by rotary evaporation and passed through a short silica gel column with dichloromethane elution to yield 420 mg (~95%) of a viscous, clear oil.
In 2 ml of dichloromethane was dissolved 300 mg (1.03 mmol) of the above dichloro ester. Triethylamine (110 mg, 1.10 mmol) was then added, and the reaction was monitored by TLC. The reaction mixture was washed successively with 5 ml of 1.0 M HCl and brine, followed by drying over anhydrous sodium sulfate. Formation of an approximately 10:1 ratio of 1 to its E isomer was indicated by 1 H NMR spectroscopy of the crude product.

Refinement
All H-atoms were placed geometrically (C-H 0.93 and 0.96 Å for aromatic and methyl H atoms respectively) and included in the refinement in the riding motion approximation with U iso (H) = 1.2U eq (C) for CH and U iso (H) = 1.5U eq (C) for CH 3 .    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 Rfactors(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.