organic compounds
4-({(Z)-5-[(Z)-3-Ethoxy-4-hydroxybenzylidene]-3-methyl-4-oxo-1,3-thiazolidin-2-ylidene}amino)benzoic acid dimethylformamide monosolvate
aDepartment of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria, bUniversity Clinic of Radiotherapy, Medical University Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria, and cInstitute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164SC, A-1060 Vienna, Austria
*Correspondence e-mail: kurt.mereiter@tuwien.ac.at
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 αvβ3 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
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Refinement
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Data collection: APEX2 (Bruker, 2008); cell 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).
Supporting information
10.1107/S1600536812047307/fk2066sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536812047307/fk2066Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536812047307/fk2066Isup3.cml
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.
C-bonded H atoms were placed in calculated positions and thereafter treated as riding, C—H = 0.95–0.99 Å, Uiso(H) = 1.2–1.5Ueq(C). O-bonded H atoms were refined with AFIX 147 of program SHELXL97 (Sheldrick, 2008), O—H = 0.84 Å, Uiso(H) = 1.5Ueq(O).
Data collection: APEX2 (Bruker, 2008); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); 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).C20H18N2O5S·C3H7NO | Z = 2 |
Mr = 471.52 | F(000) = 496 |
Triclinic, P1 | Dx = 1.386 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.7532 (3) Å | Cell parameters from 9007 reflections |
b = 9.3081 (3) Å | θ = 2.2–30.0° |
c = 15.6969 (3) Å | µ = 0.19 mm−1 |
α = 86.390 (2)° | T = 100 K |
β = 89.813 (2)° | Prism, yellow |
γ = 87.656 (2)° | 0.53 × 0.35 × 0.24 mm |
V = 1129.61 (6) Å3 |
Bruker Kappa APEXII CCD diffractometer | 6537 independent reflections |
Radiation source: fine-focus sealed tube | 5993 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.024 |
ϕ and ω scans | θmax = 30.0°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −10→10 |
Tmin = 0.89, Tmax = 0.96 | k = −13→13 |
29040 measured reflections | l = −22→22 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.033 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.094 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0516P)2 + 0.4019P] where P = (Fo2 + 2Fc2)/3 |
6537 reflections | (Δ/σ)max = 0.002 |
304 parameters | Δρmax = 0.51 e Å−3 |
0 restraints | Δρmin = −0.22 e Å−3 |
C20H18N2O5S·C3H7NO | γ = 87.656 (2)° |
Mr = 471.52 | V = 1129.61 (6) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.7532 (3) Å | Mo Kα radiation |
b = 9.3081 (3) Å | µ = 0.19 mm−1 |
c = 15.6969 (3) Å | T = 100 K |
α = 86.390 (2)° | 0.53 × 0.35 × 0.24 mm |
β = 89.813 (2)° |
Bruker Kappa APEXII CCD diffractometer | 6537 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 5993 reflections with I > 2σ(I) |
Tmin = 0.89, Tmax = 0.96 | Rint = 0.024 |
29040 measured reflections |
R[F2 > 2σ(F2)] = 0.033 | 0 restraints |
wR(F2) = 0.094 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.51 e Å−3 |
6537 reflections | Δρmin = −0.22 e Å−3 |
304 parameters |
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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.41930 (3) | 0.65538 (2) | 0.349946 (14) | 0.01698 (6) | |
O1 | 0.80606 (9) | 0.38102 (8) | 0.35244 (5) | 0.02040 (14) | |
O2 | 0.37560 (9) | 0.96319 (8) | 0.62843 (5) | 0.02005 (14) | |
O3 | 0.65049 (10) | 0.96754 (8) | 0.73138 (5) | 0.02233 (15) | |
H3o | 0.5526 | 1.0091 | 0.7342 | 0.033* | |
O4 | −0.39179 (10) | 0.90766 (9) | 0.17578 (5) | 0.02725 (17) | |
O5 | −0.23650 (9) | 1.02278 (8) | 0.07406 (5) | 0.02368 (16) | |
H5o | −0.3306 | 1.0689 | 0.0647 | 0.036* | |
N1 | 0.57050 (10) | 0.44691 (8) | 0.26982 (5) | 0.01658 (15) | |
N2 | 0.33188 (11) | 0.54753 (9) | 0.19732 (5) | 0.01936 (16) | |
C1 | 0.43011 (12) | 0.54409 (10) | 0.26183 (6) | 0.01595 (16) | |
C2 | 0.60871 (14) | 0.34431 (11) | 0.20524 (7) | 0.02270 (19) | |
H2A | 0.7153 | 0.2885 | 0.2205 | 0.034* | |
H2B | 0.6232 | 0.3965 | 0.1496 | 0.034* | |
H2C | 0.5133 | 0.2789 | 0.2022 | 0.034* | |
C3 | 0.67482 (12) | 0.45592 (10) | 0.33963 (6) | 0.01610 (16) | |
C4 | 0.60700 (12) | 0.56946 (10) | 0.39437 (6) | 0.01610 (16) | |
C5 | 0.69539 (12) | 0.59362 (10) | 0.46550 (6) | 0.01749 (17) | |
H5 | 0.7951 | 0.5316 | 0.4740 | 0.021* | |
C6 | 0.67052 (12) | 0.69420 (10) | 0.53172 (6) | 0.01676 (17) | |
C7 | 0.52167 (12) | 0.78354 (10) | 0.54232 (6) | 0.01713 (17) | |
H7 | 0.4277 | 0.7816 | 0.5037 | 0.021* | |
C8 | 0.51260 (12) | 0.87446 (10) | 0.60936 (6) | 0.01695 (17) | |
C9 | 0.65368 (12) | 0.87976 (10) | 0.66581 (6) | 0.01783 (17) | |
C10 | 0.79983 (13) | 0.79211 (11) | 0.65505 (6) | 0.01950 (18) | |
H10 | 0.8948 | 0.7954 | 0.6929 | 0.023* | |
C11 | 0.80769 (12) | 0.69964 (10) | 0.58921 (6) | 0.01877 (18) | |
H11 | 0.9078 | 0.6389 | 0.5829 | 0.023* | |
C12 | 0.22371 (12) | 0.96318 (10) | 0.57563 (6) | 0.01843 (17) | |
H12A | 0.1783 | 0.8652 | 0.5764 | 0.022* | |
H12B | 0.2514 | 0.9948 | 0.5159 | 0.022* | |
C13 | 0.09223 (13) | 1.06669 (11) | 0.61232 (7) | 0.02253 (19) | |
H13A | 0.0657 | 1.0338 | 0.6713 | 0.034* | |
H13B | −0.0134 | 1.0705 | 0.5780 | 0.034* | |
H13C | 0.1392 | 1.1629 | 0.6115 | 0.034* | |
C14 | 0.18954 (12) | 0.64677 (10) | 0.18805 (6) | 0.01736 (17) | |
C15 | 0.03664 (13) | 0.62483 (11) | 0.23377 (6) | 0.02102 (19) | |
H15 | 0.0308 | 0.5477 | 0.2762 | 0.025* | |
C16 | −0.10619 (13) | 0.71632 (11) | 0.21680 (6) | 0.02002 (18) | |
H16 | −0.2100 | 0.7017 | 0.2479 | 0.024* | |
C17 | −0.09940 (12) | 0.82963 (10) | 0.15451 (6) | 0.01648 (17) | |
C18 | 0.05412 (12) | 0.85138 (10) | 0.10947 (6) | 0.01830 (17) | |
H18 | 0.0599 | 0.9289 | 0.0673 | 0.022* | |
C19 | 0.19814 (12) | 0.76057 (11) | 0.12589 (6) | 0.01939 (18) | |
H19 | 0.3021 | 0.7757 | 0.0950 | 0.023* | |
C20 | −0.25683 (12) | 0.92308 (11) | 0.13672 (6) | 0.01868 (18) | |
O6 | −0.49662 (10) | 1.18732 (8) | 0.02984 (5) | 0.02426 (16) | |
N3 | −0.76655 (11) | 1.27974 (10) | 0.05269 (6) | 0.02176 (17) | |
C21 | −0.63956 (13) | 1.18080 (11) | 0.06532 (6) | 0.02044 (18) | |
H21 | −0.6593 | 1.1002 | 0.1038 | 0.025* | |
C22 | −0.74498 (16) | 1.40627 (12) | −0.00518 (7) | 0.0282 (2) | |
H22A | −0.7384 | 1.4918 | 0.0279 | 0.042* | |
H22B | −0.8436 | 1.4184 | −0.0442 | 0.042* | |
H22C | −0.6384 | 1.3938 | −0.0381 | 0.042* | |
C23 | −0.92669 (15) | 1.27171 (13) | 0.10088 (8) | 0.0296 (2) | |
H23A | −0.9239 | 1.1831 | 0.1381 | 0.044* | |
H23B | −1.0242 | 1.2713 | 0.0613 | 0.044* | |
H23C | −0.9399 | 1.3553 | 0.1357 | 0.044* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.01676 (11) | 0.01661 (11) | 0.01742 (11) | 0.00188 (8) | −0.00169 (8) | −0.00148 (8) |
O1 | 0.0160 (3) | 0.0205 (3) | 0.0241 (3) | 0.0017 (2) | −0.0018 (3) | 0.0007 (3) |
O2 | 0.0156 (3) | 0.0244 (3) | 0.0204 (3) | 0.0021 (3) | −0.0045 (2) | −0.0046 (3) |
O3 | 0.0187 (3) | 0.0284 (4) | 0.0204 (3) | 0.0015 (3) | −0.0037 (3) | −0.0071 (3) |
O4 | 0.0177 (3) | 0.0369 (4) | 0.0265 (4) | 0.0031 (3) | 0.0047 (3) | −0.0001 (3) |
O5 | 0.0171 (3) | 0.0238 (4) | 0.0289 (4) | 0.0042 (3) | 0.0005 (3) | 0.0049 (3) |
N1 | 0.0170 (4) | 0.0158 (3) | 0.0168 (3) | 0.0017 (3) | −0.0013 (3) | −0.0016 (3) |
N2 | 0.0195 (4) | 0.0195 (4) | 0.0187 (4) | 0.0026 (3) | −0.0031 (3) | −0.0005 (3) |
C1 | 0.0158 (4) | 0.0148 (4) | 0.0170 (4) | −0.0002 (3) | 0.0000 (3) | 0.0007 (3) |
C2 | 0.0264 (5) | 0.0214 (4) | 0.0203 (4) | 0.0046 (4) | −0.0009 (4) | −0.0053 (3) |
C3 | 0.0157 (4) | 0.0153 (4) | 0.0172 (4) | −0.0025 (3) | −0.0001 (3) | 0.0013 (3) |
C4 | 0.0151 (4) | 0.0154 (4) | 0.0176 (4) | −0.0013 (3) | −0.0001 (3) | 0.0006 (3) |
C5 | 0.0160 (4) | 0.0176 (4) | 0.0187 (4) | −0.0014 (3) | −0.0006 (3) | 0.0007 (3) |
C6 | 0.0158 (4) | 0.0176 (4) | 0.0168 (4) | −0.0021 (3) | −0.0013 (3) | 0.0009 (3) |
C7 | 0.0150 (4) | 0.0191 (4) | 0.0172 (4) | −0.0024 (3) | −0.0030 (3) | 0.0011 (3) |
C8 | 0.0147 (4) | 0.0184 (4) | 0.0175 (4) | −0.0018 (3) | −0.0012 (3) | 0.0011 (3) |
C9 | 0.0168 (4) | 0.0206 (4) | 0.0162 (4) | −0.0030 (3) | −0.0015 (3) | −0.0001 (3) |
C10 | 0.0159 (4) | 0.0241 (4) | 0.0184 (4) | −0.0011 (3) | −0.0040 (3) | −0.0005 (3) |
C11 | 0.0156 (4) | 0.0211 (4) | 0.0194 (4) | 0.0000 (3) | −0.0025 (3) | 0.0003 (3) |
C12 | 0.0155 (4) | 0.0204 (4) | 0.0194 (4) | −0.0010 (3) | −0.0038 (3) | −0.0007 (3) |
C13 | 0.0184 (4) | 0.0230 (5) | 0.0262 (5) | 0.0011 (3) | −0.0025 (4) | −0.0029 (4) |
C14 | 0.0176 (4) | 0.0187 (4) | 0.0158 (4) | 0.0010 (3) | −0.0037 (3) | −0.0021 (3) |
C15 | 0.0227 (5) | 0.0222 (4) | 0.0175 (4) | 0.0000 (3) | 0.0003 (3) | 0.0032 (3) |
C16 | 0.0185 (4) | 0.0234 (4) | 0.0180 (4) | −0.0016 (3) | 0.0024 (3) | 0.0006 (3) |
C17 | 0.0148 (4) | 0.0189 (4) | 0.0158 (4) | −0.0003 (3) | −0.0004 (3) | −0.0023 (3) |
C18 | 0.0163 (4) | 0.0189 (4) | 0.0193 (4) | −0.0002 (3) | 0.0006 (3) | 0.0019 (3) |
C19 | 0.0157 (4) | 0.0210 (4) | 0.0210 (4) | 0.0001 (3) | 0.0012 (3) | 0.0017 (3) |
C20 | 0.0163 (4) | 0.0214 (4) | 0.0186 (4) | 0.0002 (3) | −0.0007 (3) | −0.0040 (3) |
O6 | 0.0219 (4) | 0.0275 (4) | 0.0226 (3) | 0.0059 (3) | −0.0010 (3) | 0.0004 (3) |
N3 | 0.0206 (4) | 0.0220 (4) | 0.0226 (4) | 0.0031 (3) | −0.0031 (3) | −0.0029 (3) |
C21 | 0.0223 (5) | 0.0210 (4) | 0.0180 (4) | 0.0021 (3) | −0.0045 (3) | −0.0018 (3) |
C22 | 0.0351 (6) | 0.0217 (5) | 0.0268 (5) | 0.0067 (4) | −0.0057 (4) | 0.0010 (4) |
C23 | 0.0212 (5) | 0.0342 (6) | 0.0344 (6) | 0.0010 (4) | 0.0011 (4) | −0.0103 (5) |
S1—C4 | 1.7564 (10) | C11—H11 | 0.9500 |
S1—C1 | 1.7793 (9) | C12—C13 | 1.5116 (14) |
O1—C3 | 1.2197 (12) | C12—H12A | 0.9900 |
O2—C8 | 1.3628 (11) | C12—H12B | 0.9900 |
O2—C12 | 1.4423 (11) | C13—H13A | 0.9800 |
O3—C9 | 1.3533 (12) | C13—H13B | 0.9800 |
O3—H3o | 0.8400 | C13—H13C | 0.9800 |
O4—C20 | 1.2200 (12) | C14—C19 | 1.3978 (13) |
O5—C20 | 1.3227 (12) | C14—C15 | 1.3993 (13) |
O5—H5o | 0.8400 | C15—C16 | 1.3852 (14) |
N1—C3 | 1.3729 (12) | C15—H15 | 0.9500 |
N1—C1 | 1.3873 (12) | C16—C17 | 1.3948 (13) |
N1—C2 | 1.4575 (12) | C16—H16 | 0.9500 |
N2—C1 | 1.2671 (12) | C17—C18 | 1.3978 (13) |
N2—C14 | 1.4118 (12) | C17—C20 | 1.4863 (13) |
C2—H2A | 0.9800 | C18—C19 | 1.3874 (13) |
C2—H2B | 0.9800 | C18—H18 | 0.9500 |
C2—H2C | 0.9800 | C19—H19 | 0.9500 |
C3—C4 | 1.4824 (13) | O6—C21 | 1.2406 (13) |
C4—C5 | 1.3475 (13) | N3—C21 | 1.3270 (13) |
C5—C6 | 1.4494 (13) | N3—C23 | 1.4539 (14) |
C5—H5 | 0.9500 | N3—C22 | 1.4563 (14) |
C6—C11 | 1.4015 (13) | C21—H21 | 0.9500 |
C6—C7 | 1.4103 (13) | C22—H22A | 0.9800 |
C7—C8 | 1.3912 (13) | C22—H22B | 0.9800 |
C7—H7 | 0.9500 | C22—H22C | 0.9800 |
C8—C9 | 1.4143 (13) | C23—H23A | 0.9800 |
C9—C10 | 1.3851 (14) | C23—H23B | 0.9800 |
C10—C11 | 1.3857 (14) | C23—H23C | 0.9800 |
C10—H10 | 0.9500 | ||
C4—S1—C1 | 91.11 (4) | C13—C12—H12B | 110.4 |
C8—O2—C12 | 117.96 (7) | H12A—C12—H12B | 108.6 |
C9—O3—H3o | 109.5 | C12—C13—H13A | 109.5 |
C20—O5—H5o | 109.5 | C12—C13—H13B | 109.5 |
C3—N1—C1 | 116.78 (8) | H13A—C13—H13B | 109.5 |
C3—N1—C2 | 121.81 (8) | C12—C13—H13C | 109.5 |
C1—N1—C2 | 121.36 (8) | H13A—C13—H13C | 109.5 |
C1—N2—C14 | 121.40 (8) | H13B—C13—H13C | 109.5 |
N2—C1—N1 | 120.85 (8) | C19—C14—C15 | 120.18 (9) |
N2—C1—S1 | 128.47 (7) | C19—C14—N2 | 118.40 (9) |
N1—C1—S1 | 110.67 (7) | C15—C14—N2 | 121.13 (9) |
N1—C2—H2A | 109.5 | C16—C15—C14 | 119.55 (9) |
N1—C2—H2B | 109.5 | C16—C15—H15 | 120.2 |
H2A—C2—H2B | 109.5 | C14—C15—H15 | 120.2 |
N1—C2—H2C | 109.5 | C15—C16—C17 | 120.75 (9) |
H2A—C2—H2C | 109.5 | C15—C16—H16 | 119.6 |
H2B—C2—H2C | 109.5 | C17—C16—H16 | 119.6 |
O1—C3—N1 | 123.42 (9) | C16—C17—C18 | 119.36 (9) |
O1—C3—C4 | 125.97 (9) | C16—C17—C20 | 119.06 (8) |
N1—C3—C4 | 110.60 (8) | C18—C17—C20 | 121.57 (8) |
C5—C4—C3 | 118.33 (8) | C19—C18—C17 | 120.46 (9) |
C5—C4—S1 | 130.83 (8) | C19—C18—H18 | 119.8 |
C3—C4—S1 | 110.81 (7) | C17—C18—H18 | 119.8 |
C4—C5—C6 | 133.55 (9) | C18—C19—C14 | 119.69 (9) |
C4—C5—H5 | 113.2 | C18—C19—H19 | 120.2 |
C6—C5—H5 | 113.2 | C14—C19—H19 | 120.2 |
C11—C6—C7 | 118.94 (9) | O4—C20—O5 | 123.61 (9) |
C11—C6—C5 | 115.68 (8) | O4—C20—C17 | 122.94 (9) |
C7—C6—C5 | 125.38 (8) | O5—C20—C17 | 113.45 (8) |
C8—C7—C6 | 119.89 (9) | C21—N3—C23 | 121.33 (9) |
C8—C7—H7 | 120.1 | C21—N3—C22 | 120.97 (9) |
C6—C7—H7 | 120.1 | C23—N3—C22 | 117.53 (9) |
O2—C8—C7 | 126.07 (9) | O6—C21—N3 | 123.87 (10) |
O2—C8—C9 | 113.74 (8) | O6—C21—H21 | 118.1 |
C7—C8—C9 | 120.18 (9) | N3—C21—H21 | 118.1 |
O3—C9—C10 | 118.26 (9) | N3—C22—H22A | 109.5 |
O3—C9—C8 | 121.99 (9) | N3—C22—H22B | 109.5 |
C10—C9—C8 | 119.74 (9) | H22A—C22—H22B | 109.5 |
C9—C10—C11 | 120.09 (9) | N3—C22—H22C | 109.5 |
C9—C10—H10 | 120.0 | H22A—C22—H22C | 109.5 |
C11—C10—H10 | 120.0 | H22B—C22—H22C | 109.5 |
C10—C11—C6 | 121.14 (9) | N3—C23—H23A | 109.5 |
C10—C11—H11 | 119.4 | N3—C23—H23B | 109.5 |
C6—C11—H11 | 119.4 | H23A—C23—H23B | 109.5 |
O2—C12—C13 | 106.71 (8) | N3—C23—H23C | 109.5 |
O2—C12—H12A | 110.4 | H23A—C23—H23C | 109.5 |
C13—C12—H12A | 110.4 | H23B—C23—H23C | 109.5 |
O2—C12—H12B | 110.4 | ||
C14—N2—C1—N1 | −179.41 (8) | O2—C8—C9—O3 | −0.99 (13) |
C14—N2—C1—S1 | −1.09 (14) | C7—C8—C9—O3 | 179.48 (9) |
C3—N1—C1—N2 | 176.75 (9) | O2—C8—C9—C10 | 178.36 (9) |
C2—N1—C1—N2 | −0.86 (14) | C7—C8—C9—C10 | −1.18 (14) |
C3—N1—C1—S1 | −1.85 (10) | O3—C9—C10—C11 | 179.38 (9) |
C2—N1—C1—S1 | −179.46 (7) | C8—C9—C10—C11 | 0.01 (14) |
C4—S1—C1—N2 | −177.56 (9) | C9—C10—C11—C6 | 0.98 (15) |
C4—S1—C1—N1 | 0.90 (7) | C7—C6—C11—C10 | −0.81 (14) |
C1—N1—C3—O1 | −176.93 (8) | C5—C6—C11—C10 | 179.63 (9) |
C2—N1—C3—O1 | 0.67 (14) | C8—O2—C12—C13 | 178.41 (8) |
C1—N1—C3—C4 | 1.95 (11) | C1—N2—C14—C19 | 108.96 (11) |
C2—N1—C3—C4 | 179.54 (8) | C1—N2—C14—C15 | −77.22 (13) |
O1—C3—C4—C5 | −0.48 (14) | C19—C14—C15—C16 | 0.23 (15) |
N1—C3—C4—C5 | −179.32 (8) | N2—C14—C15—C16 | −173.49 (9) |
O1—C3—C4—S1 | 177.69 (8) | C14—C15—C16—C17 | 0.20 (15) |
N1—C3—C4—S1 | −1.15 (9) | C15—C16—C17—C18 | −0.59 (15) |
C1—S1—C4—C5 | 178.01 (10) | C15—C16—C17—C20 | 178.47 (9) |
C1—S1—C4—C3 | 0.14 (7) | C16—C17—C18—C19 | 0.56 (14) |
C3—C4—C5—C6 | 178.92 (9) | C20—C17—C18—C19 | −178.48 (9) |
S1—C4—C5—C6 | 1.18 (17) | C17—C18—C19—C14 | −0.13 (15) |
C4—C5—C6—C11 | −170.63 (10) | C15—C14—C19—C18 | −0.27 (15) |
C4—C5—C6—C7 | 9.84 (17) | N2—C14—C19—C18 | 173.62 (9) |
C11—C6—C7—C8 | −0.36 (13) | C16—C17—C20—O4 | 1.91 (15) |
C5—C6—C7—C8 | 179.15 (9) | C18—C17—C20—O4 | −179.04 (10) |
C12—O2—C8—C7 | 0.83 (14) | C16—C17—C20—O5 | −177.34 (9) |
C12—O2—C8—C9 | −178.67 (8) | C18—C17—C20—O5 | 1.71 (13) |
C6—C7—C8—O2 | −178.13 (9) | C23—N3—C21—O6 | −175.35 (10) |
C6—C7—C8—C9 | 1.34 (14) | C22—N3—C21—O6 | −0.22 (16) |
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 |
Symmetry code: (i) −x, −y+2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C20H18N2O5S·C3H7NO |
Mr | 471.52 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 100 |
a, b, c (Å) | 7.7532 (3), 9.3081 (3), 15.6969 (3) |
α, β, γ (°) | 86.390 (2), 89.813 (2), 87.656 (2) |
V (Å3) | 1129.61 (6) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.19 |
Crystal size (mm) | 0.53 × 0.35 × 0.24 |
Data collection | |
Diffractometer | Bruker Kappa APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2008) |
Tmin, Tmax | 0.89, 0.96 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 29040, 6537, 5993 |
Rint | 0.024 |
(sin θ/λ)max (Å−1) | 0.703 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.033, 0.094, 1.02 |
No. of reflections | 6537 |
No. of parameters | 304 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.51, −0.22 |
Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), Mercury (Macrae et al., 2006), PLATON (Spek, 2009) and publCIF (Westrip, 2010).
D—H···A | D—H | H···A | D···A | D—H···A |
O5—H5o···O6 | 0.84 | 1.73 | 2.5529 (10) | 167.1 |
O3—H3o···O4i | 0.84 | 2.05 | 2.7386 (11) | 138.9 |
Symmetry code: (i) −x, −y+2, −z+1. |
Acknowledgements
The X-ray centre of the Vienna University of Technology is acknowledged for providing access to the single-crystal diffractometer.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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 via αvβ3 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 O3phenol—H3o···O4carboxyl(-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.