S. Shah, B. Singh / Bioorg. Med. Chem. Lett. 22 (2012) 5388–5391
5391
X
X
X
X
H2N
O
NH3
O
O
H2N
NH2
H
II
H2N
NH3
H2N
NH2
H
H
O
O
S
OH
O
H
S
HN
NH
X
X
S
NH
NH
X
I
S
3
X
III
Scheme 5. Plausible mechanism of urea/thiourea catalyzed Knoevenagel reaction.
26. Safonov, I. G.; Heerding, D. A.; Keenan, R. M.; Price, A. T.; Erickson-Muller, C. L.;
Hopson, C. B.; Levin, J. L.; Lord, K. A.; Tapley, P. M. Bioorg. Med. Chem. Lett. 2006,
16, 1212.
of the experimental procedure, avoidance of toxic, moisture sensi-
tive catalysts and volatile solvents. Also no hazardous by-products
are formed during reaction work-up.
27. Zhou, J. F.; Zhu, F. X.; Song, Y. Z.; Zhu, Y. L. Arkivoc 2006, 14, 175.
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Chem. Lett. 2006, 16, 3859; (b) Song, Y.; Connor, D. T.; Doubleday, R.; Sorenson,
R. J.; Sercel, A.; Unangst, P. C.; Roth, B. D.; Gilbertsen, R. B.; Chan, K.; Schrier, D.
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Lee, G.; Liu, J.; Peterson, M. G.; Tonn, G. R.; Ye, Q. Y.; Walker, N. P. C.; Wang, Z. J.
Med. Chem. 2006, 1034, 49.
Acknowledgements
The authors are thankful to the University Grant Commission
(UGC) New Delhi, for financial assistance and Sophisticated Analyt-
ical Instrumentation Facility (SAIF) Panjab University, Chandigarh
for spectral analysis.
30. Lohray, B. B.; Bhushan, V.; Rao, P. B.; Madhavan, G. R.; Murali, N.; Rao, K. N.;
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38. General procedure for the synthesis of 5-arylidenethiazolidine-2,4-diones and 5-
References and notes
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arylidene-2-thioxothiazolidin-4-ones:
A mixture of aldehyde (1 mmol), 2,4-
thiazolidinediones/2-thioxothiazolidin-4-ones (1 mmol) using 10 mol % urea/
thiourea as catalyst was condensed at 110 °C on oil bath under solvent-free
reaction conditions. After completion of the reaction as indicated by TLC, the
crude product was cooled, washed with water (10 mL), filtered and
recrystallization from ethanol: DMF to afford 3a–ab.
General procedure for the Synthesis of 3 via addition–elimination reaction: A
mixture of urea-adduct
4 (1 mmol)/azomethine 5 (1 mmol) and 2,4-
thiazolidinediones/2-thioxothiazolidin-4-ones (1 mmol) was heated at 110 °C
on oil bath. Reaction progress was monitored by TLC, after reaction completion
crude product was cooled, washed with water (10 mL), filtered and
recrystallization from ethanol: DMF to afford 3a–ab.
The physical data of known compounds were found to be identical with those
28–31
reported in the literature.
provided below.
The Spectral data for selected products are
5-benzylidene-2,4 –thiazolidinedione (Table 2, entry 1): 1H NMR (DMSO-d6,
400 MHz, ppm): d = 12.66 (s, 1H), 7.80 (s, 1H), 7.69–7.64 (m, 5H); 13C NMR
(DMSO-d6, 125 MHz, ppm): d = 114.8, 128.4, 131.7, 132.3, 132.6, 133. 8, 135.5,
171.4, 173.5 (C@O).
5-(4-Methoxybenzylidene)-2,4–thiazolidinedione (Table 2, entry 3): 1H NMR
(DMSO-d6, 400 MHz, ppm): d = 12.51 (s, 1H), 7.76 (s, 1H), 7.69–7.54 (m, 4H),
3,75 (s, 3H); 13C NMR (DMSO-d6, 125 MHz, ppm): d = 55.5, 116.8, 129.3, 131.5,
132.8, 133.6, 134.8, 135.5, 171.2, 173.7 (C@O).
5-(4-Chlorobenzylidene)-4-thioxo-thiazolidine-2-one (Table 2, entry 19): 1H NMR
(DMSO-d6, 400 MHz, ppm): d = 13.86 (s, 1H, NH); 8.12 (s, 1H); 7.69–7.57 (m,
4H); 13C NMR (DMSO-d6, 125 MHz, ppm): d = 129.5, 131.28, 132.8, 1334.3,
134.3, 135.0, 171.3, (C@O), 195. 9 (C@S).
5-(4-Bromobenzylidene)-4-thioxo-thiazolidine-2-one (Table 2, entry 20) 1H NMR
(DMSO-d6, 400 MHz, ppm): d = 13.55 (s, 1H), 8.09 (s, 1H), 7.88–7.63 (m, 4H);
13C NMR (DMSO-d6, 125 MHz, ppm): d = 127.1, 131.8, 132.8, 133.7, 133.8134.8,
134.7, 135.9; 171.0 (C@O), 196.2 (C@S).
5-(2,4-Dichlorobenzylidene)-4-thioxo-thiazolidine-2-one (Table 2, entry 25): 1H
NMR (DMSO-d6, 400 MHz, ppm): d = 13.67 (s, 1H), d = 8.30 (s, 1H), 7.85–7.66
(m, 3H); 13C NMR (DMSO-d6, 125 MHz, ppm): d = 129. 3, 130.5, 131.8, 132.1,
133.7, 134.9, 137.1, 138.7; 171.4 (C@O); 196.5 (C@S).
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