204 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Radi et al.
extracted with ethyl acetate; organic phases were collected,
washed with NH4Cl, dried over Na2SO4. After removal of
the solvent, the crude mixture was purified by flash chro-
matography (EtOAc/hexane, 1:4) to give the pure products.
(Z)-3-benzyl-5-benzylidene-2-thioxothiazolidin-4-one (3c).
(Yield 10%) Yellow solid; 1H NMR (400 MHz, CDCl3) 7.79
(1H,s), 7.55-7.26 (10H, m), 5.31 (2H, s) ppm. 13C NMR
(CDCl3, 100 MHz) 47.5, 122.8, 128.0, 128.3, 128.9, 129.3,
130.6, 131.0, 133.1, 133.2, 135.0, 167.8, 192.8 ppm. MS
(ESI): m/z 312 [M+H]+, Anal. (C17H13NOS2) C, H, N.
2-(2-((Z)-5-(3-fluorobenzylidene)-4-oxo-2-thioxothiazo-
lidin-3-yl)ethyl)isoindoline-1,3-dione (3d). (Yield 27%)
Yellow solid; 1H NMR (400 MHz, CDCl3) 7.74-7.72 (2H,
m), 7.62-7.61 (2H, m), 7.52 (1H, s), 7.39-7.32 (1H, q),
7.20-7.16 (1H, d), 7.09-7.06 (2H, m), 4.40-4.38 (2H, t),
4.07-4.00 (2H, t) ppm. 13C NMR (100 MHz, CDCl3) 193.3,
168.1, 167.7, 164.2, 161.7, 135.4, 131.9, 131.6, 130.9, 126.4,
124.2, 117.8, 117.6, 117.1, 116.9, 43.1, 35.3 ppm. MS (ESI):
m/z 413 [M+H]+; Anal. (C20H13FN2O3S2) C, H, N.
(1H, s), 7.3-7.1 (5H, m), 6.76 (1H, m), 6.52 (1H, m),
4.27-4.23 (2H, t, J ) 7.9 Hz), 2.95-2.91 (2H, t, J ) 7.9
Hz) ppm. 13C NMR (100 MHz, CDCl3) 194.3, 167.3, 150.2,
147.0, 137.6, 129.0, 128.6, 126.8, 120.9, 118.6, 118.3, 113.5,
45.6, 33.0 ppm. MS (ESI): m/z 316 [M+H]+, 338 [M+Na]+;
Anal. (C16H13NO2S2) C, H, N.
(Z)-3-phenethyl-5-((pyridin-3-yl)methylene)-2-thioxothi-
azolidin-4-one (11c). HPLC tR 3.42 min. Yellow solid. Mp
1
138-140 °C. H NMR (400 MHz, CDCl3) 8.69 (1H, s),
8-57-8.56 (1H, d, J ) 4.4 Hz), 7.70-7.68 (1H, d, J ) 7.9
Hz), 7.59 (1H, s), 7.36-7.33 (1H, dd, J ) 4.7 Hz, J ) 7.9
Hz), 7.26-7.16 (5H, m), 4.28-4.24 (2H, t, J ) 7.9),
2.95-2.91 (2H, t, J ) 7.9 Hz) ppm. 13C NMR (100 MHz,
CDCl3) 192.0, 167.1, 151.9, 150.8, 137.3, 136.3, 129.4,
128.9, 128.8, 128.7, 126.9, 125.5, 124.0, 45.8, 32.9 ppm.
MS (ESI): m/z 327 [M+H]+, 449 [M+Na]+; Anal.
(C17H14N2OS2) C, H, N.
(Z)-5-((naphthalen-3-yl)methylene)-3-phenethyl-2-
thioxothiazolidin-4-one (11d). HPLC tR 8.23 min. Yellow
solid. Mp 174-176 °C. 1H NMR (400 MHz, CDCl3)
7.90-7.79 (5H, m), 7.53-7.46 (3H, m), 7.29-7.19 (5H, m),
4.30-4.26 (2H, t, J ) 7.9 Hz), 2.98-2.94 (2H, t, J ) 7.9
Hz) ppm. 13C NMR (100 MHz, CDCl3) 193.1, 167.5, 137.6,
133.9, 133.2, 132.1, 130.8, 129.2, 129.0, 128.9, 128.7, 128.3,
127.8, 127.2, 126.8, 126.2, 45.7, 33.0 ppm. MS (ESI): m/z
376 [M+H]+; Anal. (C22H17NOS2) C, H, N.
(Z)-5-(3-bromobenzylidene)-3-phenethyl-2-thioxothia-
zolidin-4-one (11e). HPLC tR 7.83 min. Yellow solid. Mp
102-104 °C. 1H NMR (400 MHz, CDCl3) 7.56-7.49 (3H,
m), δ 7.36-7.13 (7H, m), δ 4.30-4.26 (2H, t, J ) 7.8 Hz),
δ 2.96-2.92 (2H, t, J ) 7.8 Hz) ppm. 13C NMR (100 MHz,
CDCl3) 192.5, 167.3, 137.3, 137.1, 135.3, 133.4, 133.1,
130.9, 130.7, 128.9, 126.9, 124.06, 123.0, 45.75, 32.93 ppm.
MS (ESI): m/z 405 [M+H]+, 427 [M+Na]+; Anal.
(C18H14BrNOS2) C, H, N.
(Z)-5-(3-bromobenzylidene)-3-benzyl-2-thioxothiazoli-
din-4-one (11f). HPLC tR 6.90 min. Yellow solid. Mp
112-113 °C. 1H NMR (400 MHz, CDCl3) δ 7.55-7.47 (3H,
m), δ 7.41-7.24 (7H, m), δ 5.25 (2H, s) ppm. 13C NMR
(100 MHz, CDCl3) 192.5, 167.6, 135.3, 134.7, 133.5, 133.2,
131.2, 130.8, 129.0, 128.8, 128.6, 128.3, 124.7, 123.5, 47.6
ppm. MS (ESI): m/z 414 [M+Na]+; Anal. (C17H12BrNOS2)
C, H, N.
(Z)-5-(3-bromobenzylidene)-3-butyl-2-thioxothiazolidin-
4-one (11g). HPLC tR 7.95 min. Yellow solid. Mp 113-115
°C. 1H NMR (400 MHz, CDCl3) 7.51-7.45 (3H, m),
7.33-7.24 (2H, m), 4.05-4.02 (2H, t, J ) 7.5 Hz),
1.61-1-59 (2H, m, J ) 7.5 Hz), 1.32-1.29 (2H, m, J )
7.5 Hz), 0.90-0.87 (3H, t, J ) 7.2 Hz) ppm. 13C NMR (100
MHz, CDCl3) 192.7, 167.5, 135.4, 133.3, 133.2, 130.7, 128.7,
124.9, 123.4, 44.6, 29.0, 20.1, 13.7 ppm. MS (ESI): m/z 356
[M+H]+; Anal. (C14H14BrNOS2) C, H, N.
(Z)-5-benzylidene-2-thioxothiazolidin-4-one (5). To a
solution of rhodanine 1b (0.15 mmol) in DMF (0.5 mL) were
added TEA (0.18 mmol) and benzaldehyde (0.15 mmol). The
mixture was heated at 110 °C under microwave irradiation
for 20 min, and then it was cooled down to room temperature.
Water was added, and the mixture was extracted with diethyl
ether; organic phases were collected, washed with NH4Cl,
dried over Na2SO4, and concentrated in vacuo. After removal
of the solvent, the crude mixture was purified by flash
chromatography (EtOAc/hexane; 1:6) to give the pure
1
product 5 in 60% yield. H NMR (400 MHz, CDCl3):
7.4-7.3 (m, 5H); 4.9 (s, 2H). 13C NMR (CDCl3): 49.3;
133.9; 128.8; 128.6; 128.5; 167.1. MS (ESI): m/z 222
[M+H]+; Anal. (C10H7NOS2) C, H, N.
One-Pot Two-Steps Microwave-Assisted Synthesis of
N-substituted 5-Arylidene-thiazol-4-ones. General Pro-
cedure. To a solution of bis(carboxymethyl)trithiocarbonate
7 (1 equiv) in DME (1.0 mL) were added TEA (1 equiv)
and the opportune amine (R1NH2, 1 equiv). The reaction
mixture was heated at 90 °C for 10 min under microwave
irradiation. After this time, the opportune aldehyde (R2CHO,
1 equiv) was added, and the mixture was heated at 110 °C
for 5 min under microwave irradiation. The reaction mixture
was evaporated to dryness, and the residue was additioned
with MeOH; the final rhodanine derivative was obtained as
a pure precipitate upon standing, isolated by filtration, washed
with hexane, and finally dried under high vacuum.
(Z)-5-(3-methoxybenzylidene)-3-phenethyl-2-thioxothi-
azolidin-4-one (11a). HPLC tR 5.92 min. Yellow solid. Mp
122-125. 1H NMR (400 MHz, CDCl3) 7.60 (1H, s),
7.34-7.18 (6H, m), 7.03-7.01 (1H, d), 6.92 (2H, s),
4.29-4.25 (2H, t, J ) 7.9 Hz), 3.79 (3H, s), 2.96-2.92 (2H,
t, J ) 7.9 Hz) ppm. 13C NMR (100 MHz, CDCl3) 193.1,
167.5, 160.1, 137.5, 134.6, 133.1, 130.4, 129.0, 128.9, 128.7,
128.6, 126.8, 123.2, 116.9, 115.2, 55.4, 45.7, 32.9 ppm. MS
(ESI): m/z 356 [M+H]+, 378 [M+Na]+; Anal.
(C19H17NO2S2) C, H, N.
(Z)-5-(3-bromobenzylidene)-3-(prop-2-ynyl)-2-thioxothi-
azolidin-4-one (11h). HPLC tR 3.44 min. Orange solid. Mp
159-161 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (1H, s), δ
7.55 (1H,s), δ 7.51-7.49 (1H, d, J ) 7.7 Hz), δ 7.35-7.34
(1H, d, J ) 7.7 Hz), δ 7.29-7.19 (1H, t, J ) 7.7 Hz), δ
4.81-4.80 (2H, d, J ) 2.1 Hz), δ 2.19-2.18 (1H, t, J ) 2.1
Hz) ppm. 13C NMR (100 MHz, CDCl3) 191.2, 166.4, 135.2,
(Z)-5-((furan-2-yl)methylene)-3-phenethyl-2-thioxothia-
zolidin-4-one (11b). HPLC tR 4.10 min. Orange solid. Mp
150-152 °C. 1H NMR (400 MHz, CDCl3) 7.63 (1H, s), 7.38