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

Rodolfo Moreno-Fuquen; Juan C Castillo; Rodrigo Abonia; Javier Ellena; Carlos A De Simone

doi:10.1107/S160053681402340X

. 2014 Nov 5;70(Pt 12):o1235–o1236. doi: 10.1107/S160053681402340X

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

Rodolfo Moreno-Fuquen ^a,^*, Juan C Castillo ^a, Rodrigo Abonia ^a, Javier Ellena ^b, Carlos A De Simone ^b

PMCID: PMC4257375 PMID: 25553018

Abstract

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.

Keywords: crystal structure; benzo[d][1,3]dioxole; 1,3-thiazolidin-4-one; biological properties; pharmacological properties; hydrogen bonding

Related literature

For biological and pharmacological properties of thiazolidin-4-one systems, see: Rojas et al. (2011 ▶); Jackson et al. (2007 ▶); Gududuru et al. (2004 ▶); Kunzler et al. (2013 ▶); Rawal et al. (2008 ▶); Barreca et al. (2002 ▶); Rawal et al. (2007 ▶); Cunico et al. (2007 ▶). For similar structures, see: Fun et al. (2011 ▶); Cunico et al. (2007 ▶). For the synthesis of heterocycles of synthetic and biological interest, see: Abonia et al. (2010 ▶); Abonia (2014 ▶); Moreno-Fuquen et al. (2014 ▶). For hydrogen bonding, see: Nardelli (1995 ▶). For hydrogen-bond graph-set motifs, see: Etter (1990 ▶).

Experimental

Crystal data

C₂₀H₂₁NO₆S
M _r = 403.44
Monoclinic,
a = 15.3098 (11) Å
b = 14.3677 (12) Å
c = 8.6546 (3) Å
β = 97.429 (4)°
V = 1887.7 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 295 K
0.25 × 0.24 × 0.12 mm

Data collection

Nonius KappaCCD diffractometer
6325 measured reflections
3845 independent reflections
2922 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.150
S = 1.03
3845 reflections
258 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO (Otwinowski & Minor, 1997 ▶) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681402340X/gg2142sup1.cif

e-70-o1235-sup1.cif^{(21.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681402340X/gg2142Isup2.hkl

e-70-o1235-Isup2.hkl^{(188.5KB, hkl)}

Click here for additional data file.^{(1.5MB, tif)}

. DOI: 10.1107/S160053681402340X/gg2142fig1.tif

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.

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S160053681402340X/gg2142fig2.tif

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.

Click here for additional data file.^{(85.2KB, tif)}

. DOI: 10.1107/S160053681402340X/gg2142fig3.tif

The formation of the title compound.

CCDC reference: 1030709

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C18H18AO1ⁱ	0.96	2.45	3.350(3)	155
C8H8BO6ⁱⁱ	0.97	2.60	3.529(2)	161

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

RMF and RA are grateful to the Universidad del Valle, Colombia, for partial financial support. JCC acknowledges his doctoral fellowship granted by COLCIENCIAS.

supplementary crystallographic information

S1. Comment

The title thiazolidin-4-one compound, C₂₀H₂₁NO₆S 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 well-known 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).

The molecular structure of (I) is shown in Fig. 1. The central thiazolidine (C9/C10/S1/C11/N1) ring is essentially planar [r.m.s. deviation for all non-H atoms = 0.0287 Å] and it forms dihedral angles of 88.25 (5)° with the methoxy-substituted benzene ring and 74.21 (4)° with the 1,3-benzodioxole ring. The 1,3-benzodioxole ring is essentially planar [r.m.s. deviation for all non-H atoms = 0.0439 Å]. The dihedral angle between the benzene and benzodioxole rings is 25.12 (8)°. Two methoxy groups attached to the benzene ring are approximately parallel to the plane of the ring and the third methoxy group forms a nearly perpendicular angle with this ring. Methoxy groups on the benzene ring, have the following values of torsion angles: -3.9 (3)°, 81.9 (2)° and -1.4 (3)°. Bond lengths and bond angles in the central thiazolidine ring are very close to those reported in similar structures (Fun et al., 2011; Cunico et al., 2007). The molecules form a one dimensional chain, through C—H···O weak interactions, (see Table 1; Nardelli, 1995). Weak C18-H18···O1 and C8-H8···O6 contacts which reinforced each other, allow the molecules to propagate, forming R⁴₄(28) edge-fused rings, along [001] (Etter, 1990), (see Fig. 2).

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 thin-layer chromatography. Then, the obtained oily material was purified by column chromatography on silica gel using a mixture of CH₂Cl₂/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].