4-({(Z)-5-[(Z)-3-Ethoxy-4-hydroxybenzylidene]-3-methyl-4-oxo-1,3-thiazolidin-2-ylidene}amino)benzoic acid dimethylformamide monosolvate

The molecular structure of the title compound, C20H18N2O5S·C3H7NO, represents an essentially planar 5-benzylidene-thiazolidine moiety (r.m.s. deviation from planarity without ring substituents = 0.095 Å) to which the 4-aminobenzoic acid fragment is inclined at 76.23 (1)°. In the crystal, the benzoic acid molecules are arranged in layers parallel to [001] which are built up from inversion dimers held together by head-to-tail phenol–carboxy O—H⋯O hydrogen bonds and head-to-tail π–π stacking interactions between the 5-benzylidene-thiazolidine moieties (ring centroid distance = 3.579 Å). These layers are separated by the dimethylformamide solvent molecules which are firmly anchored via a short O—H⋯O hydrogen bond [O⋯O = 2.5529 (10) Å] donated by the –COOH group.

The molecular structure of the title compound, C 20 H 18 N 2 O 5 SÁ-C 3 H 7 NO, represents an essentially planar 5-benzylidenethiazolidine moiety (r.m.s. deviation from planarity without ring substituents = 0.095 Å ) to which the 4-aminobenzoic acid fragment is inclined at 76.23 (1) . In the crystal, the benzoic acid molecules are arranged in layers parallel to [001] which are built up from inversion dimers held together by head-totail phenol-carboxy O-HÁ Á ÁO hydrogen bonds and head-totailstacking interactions between the 5-benzylidenethiazolidine moieties (ring centroid distance = 3.579 Å ). These layers are separated by the dimethylformamide solvent molecules which are firmly anchored via a short O-HÁ Á ÁO hydrogen bond [OÁ Á ÁO = 2.5529 (10) Å ] donated by the -COOH group.   Table 1 Hydrogen-bond geometry (Å , ). The X-ray centre of the Vienna University of Technology is acknowledged for providing access to the single-crystal diffractometer.

Experimental
Although the compound 1 (Fig. 3) and its bioactivity was already described (Dayam et al.;2006), a synthesis was not reported. In the present work 1 was synthesized in good yield according to the reaction scheme shown in Fig. 3. A 40% aqueous solution of methylamine (13 g) was added dropwise at 5-7 °C to a solution of 2 (see Fig. 3; 5 g, 28 mmol) in supplementary materials water (110 ml) and stirred for ~2.5 h with gradual warming to room temperature. The aqueous solution was extracted three times with 80 ml portions of EtOAc and freed from residual EtOAc in a rotary evaporator under vacuum at 50 °C.
The solution was cooled to 5 °C and acidified with 2 M HCl to pH 3. The resulting precipitate was filtered, thoroughly washed with cold water, and dissolved in EtOAc (250 ml). The organic layer was washed with brine, dried (Na 2 SO 4 ) and concentrated to give 3.94 g (67%) of 3 (Fig. 3) as colorless solid; m.p. >170 °C (dec.). A solution of compound 3 (3.94 g, 19 mmol) in dry dioxane (60 ml) was refluxed with methyl bromoacetate (2.1 ml, 23 mmol) for 22 h. The solution was concentrated and the resulting yellow solid was dissolved in 0.1 M NaOH (100 ml). The solution was washed twice with Et 2 O (100 ml) and acidified with 2M HCl. The product was filtered off and dissolved in 1:1 EtOAc-MeOH (300 ml). The organic layer was dried (Na 2 SO 4 ) and concentrated to afford compound 4 (Fig. 3)  oxy-4-hydroxybenzaldehyde (12 g, 72 mmol) and sodium acetate (9.8 g, 120 mmol) in glacial acetic acid (300 ml) was refluxed for 4 d. Acetic acid was removed at 140 °C and the suspension was kept at 140 °C over night. After cooling to room temperature, acetic acid was added (100 ml) and the suspension was poured into water (1 L) and the resulting precipitate was filtered, washed with water and dried. The residue was crystallized from acetic acid, washed with acetone and dried to give 13 g (54%) of the title compound 1 (Fig. 3)     Reaction scheme for the synthesis of 1. where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.002 Δρ max = 0.51 e Å −3 Δρ min = −0.22 e Å −3

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > 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 S1 0.41930 (