Crystal structure of (±)-3-[(benzo[d][1,3]dioxol-5-yl)methyl]-2-(3,4,5-trimethoxyphenyl)-1,3-thiazolidin-4-one

In the title thiazolidine-4-one derivative, C20H21NO6S, the central thiazolidine ring is essentially planar (r.m.s. deviation for all non-H atoms = 0.0287 Å) and forms a dihedral angle of 88.25 (5)° with the methoxy-substituted benzene ring and 74.21 (4)° with the 1,3-benzodioxole ring. The heterocyclic ring (with two O atoms) fused to benzene ring adopts an envelope conformation with the non-ring-junction C atom as the flap. In the crystal, the molecules are linked into chains along [001] through weak C—H⋯O interactions, forming R 4 4(28) edge-fused rings.


S1. Comment
The title thiazolidin-4-one compound, C 20 H 21 NO 6 S belongs to a class of important heterocycles that have attracted considerable attention because of their biological and pharmacological properties. Their structures are present in a wellknown group of patented drugs and substances which possess antimalarial (Rojas et al., 2011), anti-arrhythmic (Jackson et al., 2007), antitumor (Gududuru et al., 2004), antifungal (Kunzler et al., 2013), antihepatitic (Rawal et al., 2008) and antiviral (Barreca et al., 2002) among other activities. There is an interest in developing biologically active molecules, with 5-membered rings containing two heteroatoms. Among them, the thiazolidin-4-ones are one of the most investigated classes of compounds (Rawal et al., 2007). Continuing with our current studies on the use of imines and imminium ions for the synthesis of heterocycles of synthetic and biological interest (Abonia et al., 2010, Abonia, 2014, Moreno-Fuquen et al., 2014, the 1,3-thiazolidin-4-one (I) was obtained from a solvent-free three-component reaction involving 3,4-(methylenedioxy)benzylamine, mercaptoacetic acid and 3,4,5-trimethoxybenzaldehyde. The reaction proceeded with the initial formation of an imine, which underwent a nucleophilic attack by the sulfur atom of the mercaptoacetic acid, followed by an intramolecular cyclization with the releasing of a molecule of water to afford the title compound (I).

S2. Experimental
Reagents and solvents for the synthesis were obtained from the Aldrich Chemical Co., and were used without additional purification. A 5 mL pyrex test tube was charged with a mixture of 3,4,5-trimethoxybenzaldehyde (145 mg, 0.74 mmol), mercaptoacetic acid (75 mg, 0.82 mmol) and 3,4-(methylenedioxy)benzylamine (111 mg, 0.74 mmol) in absence of solvent. The mixture was heated in an oil bath at 120° C for 20 min until the starting materials were no longer detected by supporting information thin-layer chromatography. Then, the obtained oily material was purified by column chromatography on silica gel using a mixture of CH 2 Cl 2 /EtOAc (10:1) as eluent. White crystals of (I) suitable for single-crystal X-ray diffraction were grown by slow evaporation, at ambient temperature and in air, from a solution in ethanol [66% yield, m.p. 395 (1) K].

S3. Refinement
All H-atoms were positioned at geometrically idealized positions [C-H = 0.93 Å for aromatic, C-H = 0.97 Å for methylene and C-H = 0.96 Å for methyl group] and refined using a riding model approximation with U iso (H) = 1.2 U eq (C), (C-H methylene and aromatic) and to 1.5 (methyl) times Ueq of the respective parent atom.

Figure 1
Molecular conformation and atom numbering scheme for the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.  Part of the crystal structure of (I), forming one-dimensional chain, along [001]. Symmetry code: (i) -x+1,-y,-z+1; (ii) x, +y,+z-1.

Figure 3
The formation of the title compound. where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.34 e Å −3 Δρ min = −0.34 e Å −3 Extinction correction: SHELXL97 (Sheldrick, 2008), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.031 (5) 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 > 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.