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

Paul Kosma; Edgar Selzer; Kurt Mereiter

doi:10.1107/S1600536812047307

. 2012 Nov 24;68(Pt 12):o3417–o3418. doi: 10.1107/S1600536812047307

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

Paul Kosma ^a, Edgar Selzer ^b, Kurt Mereiter ^c,^*

PMCID: PMC3589002 PMID: 23476238

Abstract

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.

Related literature

For bioactive compounds based on the 4-thiazolidinone scaffold of the title compound, see: Ottanà et al. (2005 ▶); Verma & Saraf (2008 ▶). For potential anticancer activity via α_vβ₃ integrin antagonistic properties of 4-thiazolidinone derivatives, see: Dayam et al. (2006 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶). For standard bond lengths, see: Allen et al. (1987 ▶). For crystal structures related to that of the title compound, see: Ottanà et al. (2005 ▶); Yavari et al. (2008 ▶); Deepthi et al. (2001 ▶); Tomaščiková et al. (2008 ▶).

Experimental

Crystal data

C₂₀H₁₈N₂O₅S·C₃H₇NO
M _r = 471.52
Triclinic,
a = 7.7532 (3) Å
b = 9.3081 (3) Å
c = 15.6969 (3) Å
α = 86.390 (2)°
β = 89.813 (2)°
γ = 87.656 (2)°
V = 1129.61 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 100 K
0.53 × 0.35 × 0.24 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.89, T _max = 0.96
29040 measured reflections
6537 independent reflections
5993 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.094
S = 1.02
6537 reflections
304 parameters
H-atom parameters constrained
Δρ_max = 0.51 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(22.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812047307/fk2066sup1.cif

e-68-o3417-sup1.cif^{(22.6KB, cif)}

Click here for additional data file.^{(319.9KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812047307/fk2066Isup2.hkl

e-68-o3417-Isup2.hkl^{(319.9KB, hkl)}

Click here for additional data file.^{(9.1KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812047307/fk2066Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5o⋯O6	0.84	1.73	2.5529 (10)	167
O3—H3o⋯O4ⁱ	0.84	2.05	2.7386 (11)	139

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Symmetry code: (i) Inline graphic .

Acknowledgments

The X-ray centre of the Vienna University of Technology is acknowledged for providing access to the single-crystal diffractometer.

supplementary crystallographic information

Comment

Compounds based on the 4-thiazolidinone scaffold received attention in recent years as bioactive agents with a broad therapeutic potential (Ottanà et al., 2005; Verma & Saraf, 2008). The title compound 1.DMF, (I), is the dimethylformamide monosolvate of a 4-thiazolidinone derivative 1, which shows significant anticancer activity viaα_vβ₃ integrin antagonistic properties (Dayam et al., 2006). The molecule of 1 consists of a planar thiazolidine ring that is substituted in 2,3,4, and 5-positions by a 4-aminobenzoic acid fragment, a methyl group, an oxo atom O1, and a 3-ethoxy-4-hydroxy-phenylmethylidene group (Fig. 1). Bond lengths and bond angles in the thiazolidine ring correspond well with related compounds, particularly with Cambridge Structural Database (Allen, 2002) refcode CAPGIK (Ottanà et al., 2005; for other structures, see: CSD BIVWUZ (Yavari et al., 2008), OGIBAH (Deepthi et al., 2001), and SIXFOV (Tomaščiková et al., 2008)), where the S1—C1 bond was typically found to be slightly longer than the S1—C4 bond (1.7793 (9) Å and 1.7564 (10) Å in 1). The ring bonds N1—C1 = 1.3873 (12) Å and N1—C3 = 1.3729 (12) Å in 1 are shorter than standard C—N single bonds and indicate some quasi-aromatic conjugation, while C3—C4 1.4824 (13) Å is longer than a typical aromatic C—C ring bond (Allen et al., 1987). The thiazolidine ring and its four substituent atoms N2, C2, O1, and C5 are nearly planar. Their r.m.s. deviation from planarity is 0.021 Å, while for the thiazolidine ring atoms this quantity is 0.007 Å. The phenylmethylidene unit is only moderately inclined to the thiazolidine ring (ring-ring inclination angle 10.85 (6)°) enabling conjugation between the two rings via the methylidene carbon C5. The bond angle C4—C5—C6 = 133.55 (9)° is large in response to the short intramolecular contact distance S1···H7 = 2.752 Å. The 4-aminobenzoic acid fragment is inclined to the thiazolidine ring by 75.01 (3)° and the bond angle at the linker atom N2 is C1—N2—C14 = 121.40 (8)°. CSD refcode CAPGIK (Ottanà et al., 2005) shows comparable trends in bond angles and conformation.

In the crystal lattice of (I) the molecules of 1 form inversion dimers with head-to-tail π–π-stacking interactions and centroid-centroid distances of 3.579 Å between the thiazolidine and the benzene rings C6 — C11 (Fig. 2). The shortest two intermolecular distances in these π–π-stacks are C3···C7(1 - x,1 - y,1 - z) = 3.2344 (13) Å and C4···C6(1 - x,1 - y,1 - z) = 3.4721 (13) Å. These π–π-stacked pairs are arranged in layers parallel to [001] held together by intermolecular hydrogen bonds O3_phenol—H3o···O4_carboxyl(-x,2 - y,1 - z) (Table 1, Fig. 2). To both sides of these layers and separating them at z≈ 0, 1, 2, etc. are the DMF solvent molecules. They are firmly attached via the strong hydrogen bonds O5—H5o···O6, O···O = 2.5529 (10) Å, donated by the COOH group of 1 to the oxygen of DMF. Likely due to this feature the title compound is stable at room temperature against desolvation.

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 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 (Na₂SO₄) 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 Et₂O (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 (Na₂SO₄) and concentrated to afford compound 4 (Fig. 3) as colorless solid (3.24 g, 68%), m.p. 198–199°C (EtOH). ¹H NMR (600 MHz, DMSO) δ 7.93 (d, 2H, J = 8.3 Hz, H-2, H-6, Ph), 7.03 (d, 2H, J = 8.3 Hz, H-3, H-5, Ph), 4.04 (s, 2H, CH₂), 3.16 (s, 3H, N—CH₃). ¹³C NMR (150 MHz, DMSO) δ 171.9 (C=O), 167.0 (COOH), 156.6 (SCN), 152.3 (C-1, Ph), 130.8 (C-2, C-6, Ph), 126.6 (C-4, Ph), 121.1 (C-3, C-5, Ph), 32.8 (CH₂), 29.2 (CH₃). HRMS (ESI) calcd for C₁₁H₁₀N₂O₃S [M—H]^-: 249.0339; found 249.0334. A solution of compound 4 (15 g, 60 mmol), 3-ethoxy-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) as yellow solid; m.p. >180 °C (dec.). ¹H NMR (600 MHz, DMSO): δ 9.78 (s, 1H, OH), 7.98 (d, 2H, J = 8.5 Hz, H-2, H-6, Ph), 7.70 (s, 1H, C-2, Ar), 7.17 (d, 1H, J = 1.9 Hz, =CH), 7.14 (d, 2H, J = 8.5 Hz, H-3, H-5, Ph), 6.95 (dd, 1H, J = 1.9, J = 8.3 Hz, H-6, Ar), 6.89 (d, 1H, J = 8.3 Hz, H-5, Ar), 4.04 (q, 2H, CH₂), 3.33 (s, 3H, N—CH₃) and 1.31 (t, 3H, CH₃). HRMS (ESI) calcd for C₂₀H₁₉N₂O₅S [M+H]⁺: 399.1009; found 399.1007. Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation at room temperature of a solution of 1 in dimethylformamide (DMF). Solvents other than DMF, like ethanol, acetone or acetic acid gave only unsuitable material.