(Z)-2-Amino-5-[2,4-dimethoxy-6-(4-methoxystyryl)benzylidene]-1,3-thiazol-4(5H)-one methanol solvate

In the crystal structure of the title compound, C21H20N2O4S·CH3OH, molecules are linked into chains by a series of intermolecular N—H⋯O, N—H⋯N and O—H⋯O hydrogen bonds. The molecular structure shows a double bond with Z geometry, connecting the thiazolone and resveratrol units. The dihedral angle between the thiazolone ring and the nearest dimethoxybenzene ring is 53.02 (7)°.

In the crystal structure of the title compound, C 21 H 20 N 2 O 4 SÁ-CH 3 OH, molecules are linked into chains by a series of intermolecular N-HÁ Á ÁO, N-HÁ Á ÁN and O-HÁ Á ÁO hydrogen bonds. The molecular structure shows a double bond with Z geometry, connecting the thiazolone and resveratrol units. The dihedral angle between the thiazolone ring and the nearest dimethoxybenzene ring is 53.02 (7) .

Comment
Many natural products possessing a trimethoxybenzene ring, e.g., colchicines, and podophyllotoxins, are potent cytotoxic agents and exert their antitumor properties by their antitubulin activity. In view of the activity of such trimethoxybenzenes, similar structurally related stilbene moieties have been studied. The trihydroxy compound, resveratrol, a naturally occurring phytoalexin (trans-3, 4, 5-trihydroxystilbene) present in grapes, berries, peanuts,and red wine [Aggarwal et al.,2004, Pettit et al., 1995 is reported to be a potential cancer chemotherapeutic agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. (Cushman et al., 1991). These observations encouraged us to design and synthesise a series of novel trimethoxy resveratrol analogs that were expected to function as potent cytotoxic agents against lung and breast cancer cells. The structural characterization of the title compound by x-ray analysis was performed to determine the geometry (E vs Z) of the double bond connecting the thiozolone ring and the resveratrol moiety, which cannot be easily determined by NMR spectroscopic analysis, and to obtain detailed information on the structural conformation of the molecule, that may be useful in structure-activity relationship (SAR) analysis. The title compound was synthesized in two steps. In step one, the formylation of (E)-1, 3-dimethoxy-5-(4-methoxystyryl)benzene with a slight excess of phosphorous oxychloride in dimethylformamide at 0 °C resulted the formation of trans-2-formyl-3, 4', 5-trimethoxystilbene. In step two, the reaction of trans-2-formyl-3, 4', 5-trimethoxystilbene with the active methelene compound, 2-aminothiazol-4(5H)-one in presence of ammonium acetate in acetic acid under microwave irradiation conditions yielded the title compound, (Z)-2-amino-5-[2,4-dimethoxy-6-(4-methoxystyryl)benzylidene]thiazol-4(5H)-one in 90% yield. The x-ray analysis studies revealed that the double bond connecting the thiazolone and resveratrol moieties has the Z geometry.
The dihedral angle between the plane of the thiazolone ring and the plane of the nearest phenyl ring is 53.02 (7)°. The crystal packing is stabilized by a series of N-H···O, N-H···N and O-H···O intermolecular hydrogen bonds.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
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 > 2σ(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.