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R. Ottanà et al. / European Journal of Medicinal Chemistry 46 (2011) 2797e2806
5.1.14. 5-(3-Phenyl-2-propen-1-ylidene)-2,4-thiazolidinedione (4e)
Yield 50%; mp 195e197 ꢃC; 1H NMR (DMSO-d6):
6.90 (dd
Anal. Calcd for C20H15NO4S: C, 65.74; H, 4.14; N, 3.83. Found C,
65.99; H, 3.89; N, 4.01.
d
J ¼ 11.4 Hz and J ¼ 15.3 Hz, 1H, vinyl); 7.26 (d J ¼ 15.3 Hz, 1H, vinyl);
7.36e7.41 (m, 3H, arom), 7.46 (d J ¼ 11.4 Hz, 1H, CH methylidene);
7.63e7.65 (m, 2H, arom); 12.40 (brs, 1H, NH exchangeable with
5.1.20. [5-({4-[2-(4-Methylphenyl)ethenyl]phenyl}methylidene)-
2,4-dioxothiazolidin-3-yl]acetic acid (5b)
D2O); 13C NMR (DMSO-d6):
d
123.8, 143.7 (vinyl), 128.1 (CH meth-
Yield 95%; mp 265e268 ꢃC; 1H NMR (DMSO-d6):
d 2.30 (s, 3H,
ylidene); 129.3, 130.1, 132.5 (CH arom); 125.3 (5eC); 135.9 (Cq
arom); 167.1, 168.0 (CO). Anal. Calcd. for C12H9NO2S: C, 62.32; H,
3.92; N, 6.06. Found C, 62.14; H, 3.64; N, 5.89.
CH3); 4.37 (s, 2H, CH2); 7.20 (m, 2H, arom); 7.24 (d J ¼ 16.5 Hz, 1H,
vinyl); 7.38 (d J ¼ 16.5 Hz, 1H, vinyl); 7.51 (m, 2H, arom); 7.63 (m,
2H, arom); 7.74 (m, 2H, arom); 7.96 (s, 1H, CH methylidene); 13C
NMR (DMSO-d6):
d 21.3 (CH3); 45.8 (CH2); 126.8, 131.4 (vinyl);
5.1.15. 5-[3-(4-Methylphenyl)-2-propen-1-ylidene]-2,4-
127.2, 127.6, 129.9, 131.2 (CH arom); 133.9 (CH methylidene); 120.9
(5eC); 132.0, 134.4, 138.2, 140.3 (Cq arom); 165.4, 167.2, 168.4 (CO).
Anal. Calcd for C21H17NO4S: C, 66.47; H, 4.52; N, 3.69. Found C,
65.98; H, 4.33; N, 3.84.
thiazolidinedione (4f)
Yield 43%; mp 170e172 ꢃC; 1H NMR (DMSO-d6):
d 2.31 (s, 3H,
CH3); 6.85 (dd J ¼ 11.1 Hz and J ¼ 15.0 Hz, 1H, vinyl); 7.21 (m, 2H,
arom); 7.23 (d J ¼ 15.0 Hz, 1H, vinyl); 7.46 (d J ¼ 11.4 Hz, 1H, CH
methylidene); 7.55 (m, 2H, arom); 12.36 (brs, 1H, NH exchangeable
5.1.21. [5-({4-[2-(4-Methoxyphenyl)ethenyl]phenyl}methylidene)-
with D2O); 13C NMR (DMSO-d6):
d
21.43 (CH3); 122.8, 143.9 (vinyl);
2,4-dioxothiazolidin-3-yl]acetic acid (5c)
128.2, 129.9 (CH arom); 132.7 (CH methylidene); 124.5 (5eC);
133.3, 140.0 (Cq arom); 167.1, 168.0 (CO). Anal. Calcd. for
C13H11NO2S: C, 63.65; H, 4.52; N, 5.71. Found C, 61.44; H, 4.31; N,
5.89.
Yield 98%; mp 262e265 ꢃC; 1H NMR (DMSO-d6):
d 3.77 (s, 3H,
CH3); 4.38 (s, 2H, CH2); 6.97 (m, 2H, CH arom); 7.15 (d J ¼ 16.5 Hz,1H,
vinyl); 7.38 (d J ¼ 16.5 Hz,1H, vinyl); 7.57e7.65 (m, 4H, arom); 7.73 (d,
2H, arom); 7.97 (s, 1H, CH methylidene); 13C NMR (DMSO-d6):
d 42.6
(CH2); 55.6 (OCH3); 125.4, 133.9 (vinyl); 114.6, 127.3, 128.5, 131.2 (CH
arom); 133.9 (CH methylidene); 120.0 (5eC); 129.6, 131.6, 140.5,
159.9 (Cq arom); 162.2,167.2,168.3 (CO). Anal. Calcd for C21H17NO5S:
C, 63.79, H, 4.33; N, 3.54. Found C, 63.45, H, 4.54; N, 3.41.
5.1.16. 5-[3-(4-Methoxyphenyl)-2-propen-1-ylidene]-2,4-
thiazolidinedione (4g)
Yield 43%; mp 190e192 ꢃC; 1H NMR (DMSO-d6):
d 3.80 (s, 3H,
CH3); 6.77 (dd J ¼ 11.4 Hz and J ¼ 15.0 Hz, 1H, vinyl); 6.98 (m, 2H,
arom); 7.24 (d J ¼ 15.0 Hz, 1H, vinyl); 7.46 (d J ¼ 11.4 Hz, 1H, CH
methylidene); 7.63 (m, 2H, arom); 12.38 (brs, 1H, NH exchangeable
5.1.22. [5-({4-[2-(4-Trifluoromethylphenyl)ethenyl]phenyl}
methylidene)-2,4-dioxothiazolidin-3-yl]acetic acid (5d)
with D2O). 13C NMR (DMSO-d6):
d
55.8 (CH3); 125.2, 141.3 (CH vinyl);
Yield 93%; mp 255e256 ꢃC; 1H NMR (DMSO-d6):
d
4.39 (s, 2H,
CH2); 7.50 (s, 2H, vinyl); 7.68 (m, 2H, arom); 7.80e7.86 (m, 4H,
arom); 7.99 (s, 1H, CH methylidene). 13C NMR (DMSO-d6):
45.4
114.2, 127.4 (CH arom); 123.9 (5eC); 131.6 (CH methylidene); 127.5,
159.8 (Cq arom); 166.5, 167.3 (CO). Anal. Calcd for C13H11NO3S: C,
59.76; H, 4.24; N, 5.36. Found C, 57.26; H, 4.11; N, 5.08.
d
(CH2); 127.4, 132.5 (vinyl); 125.6, 126.5, 126.9, 130.8 (CH arom);
121.3 (5eC); 133.6 (CH methylidene); 124.8 (CF3 JCF ¼ 270.3 Hz);
130.5, 134.6, 138.2, 140.3 (Cq arom); 164.4, 176.8, 173.1 (CO). Anal.
Calcd for C21H14F3NO4S: C, 58.20; H, 3.26; N, 3.23. Found C, 58.44;
H, 2.99; N, 3.55.
5.1.17. 5-[3-(4-Trifluoromethylphenyl)-2-propen-1-ylidene]-2,4-
thiazolidinedione (4h)
Yield 43%; mp 218e220 ꢃC; 1H NMR (DMSO-d6):
d 7.12 (dd
J ¼ 11.4 Hz and J ¼ 15.0 Hz, 1H, vinyl); 7.38 (d J ¼ 15.0 Hz, 1H, vinyl);
7.52 (d J ¼ 11.4 Hz, 1H, CH methylidene); 7.76 (m, 2H, arom); 7.91
5.1.23. [2,4-dioxo-5-(3-phenyl-2-propen-1-ylidene)thiazolidin-3-
(m, 2H, arom); 12.50 (brs, 1H, NH); 13C NMR (DMSO-d6):
d
126.5,
yl]acetic acid (5e)
141.6 (vinyl); 131.7 (CH methylidene); 126.1, 128.8 (CH arom); 127.2
(5eC); 139.9 (Cq arom), 129.7 (C-CF3 JCF ¼ 33.0 Hz), 124.6 (CF3
JCF ¼ 270.0 Hz); 167.2, 168.0 (CO). Anal. Calcd for C13H8F3NO2S: C,
52.17; H, 2.69; N, 4.68. Found C, 52.42; H, 2.72; N, 4.44.
Yield 93%; mp 215e217 ꢃC; 1H NMR (DMSO-d6):
d 4.33 (s, 2H,
CH2); 7.03 (dd J ¼ 11.7 Hz and J ¼ 15.6 Hz, 1H, vinyl); 7.35e7.41 (m,
4H, arom and vinyl); 7.66e7.70 (m, 3H, arom and CH methylidene);
13C NMR (DMSO-d6):
d 41.2 (CH2); 122.0, 142.0 (vinyl); 121.5 (5eC);
126.4 (CH methylidene); 127.2, 129.4, 130.3 (CH arom); 139.9 (Cq
arom); 165.0, 167.1, 168.0 (CO). Anal. Calcd for C14H11NO4S: C, 58.12;
H, 3.83; N, 4.84. Found C, 57.99; H, 3.63; N, 4.73.
5.1.18. General method for the synthesis of [5-{[4-(2-arylethenyl)
phenyl]methylidene}-2,4-dioxothiazolidin-3-yl]acetic acids (5aed)
and {2,4-dioxo-5-[3-phenyl-2-propen-1-ylidene]thiazolidin-3-yl}
acetic acids (5eeh)
5.1.24. {5-[3-(4-Methylphenyl)-2-propen-1-ylidene]-2,4-
A mixture of 4 (10 mmol), methyl bromoacetate (6.12 g,
40 mmol) and potassium carbonate (5.53 g, 40 mmol) in acetone
(150 mL) was refluxed for 24 h. The solvent was evaporated under
reduced pressure. The solid residue was washed with H2O and then
refluxed in glacial AcOH (40 mL) and HCl 12N (10 mL) for 2 h. After
evaporation in vacuo, the residue was refluxed again with AcOH
(40 mL) and HCl (10 mL) for 2 h. After evaporation in vacuo, the
crude solid was washed with H2O and crystallized from ethanol
providing pure carboxylic acids 5.
dioxothiazolidin-3-yl}acetic acid (5f)
Yield 93%; mp 190e193 ꢃC; 1H NMR (DMSO-d6):
d 2.32 (s, 3H,
CH3); 4.33 (s, 2H, CH2); 6.96 (dd J ¼ 11.4 Hz and J ¼ 15.3 Hz, 1H,
vinyl); 7.23 (m, 2H, arom); 7.34 (d J ¼ 15.3 Hz,1H, vinyl); 7.58 (m, 2H,
arom); 7.67 (d J ¼ 11.4 Hz, 1H, CH methylidene); 13C NMR (DMSO-
d6): d 21.5 (CH3); 42.6 (CH2); 122.6, 145.3 (vinyl); 121.4 (5eC); 134.9
(CH methylidene); 128.4, 130.0 (CH arom); 133.2, 140.5 (Cq arom);
164.9,167.1,168.3 (CO). Anal. Calcd for C15H13NO4S: C, 59.39; H, 4.32;
N, 4.62. Found C, 59.11; H, 4.12; N, 4.44.
5.1.19. [2,4-Dioxo-5-{[4-(2-phenylethenyl)phenyl]methylidene}
5.1.25. {5-[3-(4-Methoxyphenyl)-2-propen-1-ylidene]-2,4-
thiazolidin-3-yl]acetic acid (5a)
dioxothiazolidin-3-yl}acetic acid (5g)
Yield 90%; mp 256e258 ꢃC; 1H NMR (DMSO-d6):
d
4.38 (s, 2H,
CH2); 7.29e7.79 (m, 11H, arom and vinyl); 7.98 (s, 1H, CH methyl-
idene); 13C NMR (DMSO-d6):
45.5 (CH2); 127.1,127.5 (vinyl); 126.4,
Yield 95%; mp 205e207 ꢃC; 1H NMR (DMSO-d6):
d 3.80 (s, 3H,
CH3); 4.32 (s, 2H, CH2); 6.87 (dd J ¼ 11.4 Hz and J ¼ 15.0 Hz, 1H,
d
vinyl); 6.97 (m, 2H, arom); 7.32 (d J ¼ 15.3 Hz, 1H, vinyl); 7.60e7.66
127.9, 128.0, 128.7, 131.3 (CH arom); 121.1 (5eC); 133.1 (CH meth-
(m, 3H, arom and CH methylidene); 13C NMR (DMSO-d6):
d 42.9
ylidene); 135.2, 134.4, 138.2 (Cq arom); 164.4, 167.6, 169.8 (CO).
(CH2); 55.7 (CH3); 121.4, 145.3 (vinyl); 120.4 (5eC); 135.3 (CH