80
J.F.C. Albuquerque et al. / Il Farmaco 54 (1999) 77–82
Table 2
Thioxoimidazolidinones: main molecular peaks and their relative intensities
No. Formula
M+ (%)
MS m/z (%)
8
9
10
11
C17H13ClN2OS 328 (3.9)
C17H13ClN2OS 328 (79.2)
C17H13FN2OS 312 (100)
C17H11Cl3N2OS 397 (1.6)
330 (1.4), 294 (23), 293 (100), 292 (31), 91 (82)
329 (40.7), 330 (28.3), 293 (48), 292 (18), 91 (100), 89 (14)
313 (25.5), 311 (80), 91 (77)
398 (1.8), 361 (100), 362 (22), 363 (64), 127 (40), 125 (87), 99 (22), 90 (27), 89 (90), 86 (37)
12
13
14
C18H15ClN2OS 342 (100)
C19H17ClN2OS 356 (40.1)
C19H18ClN3OS 371 (100)
343 (46.0), 344 (41.2), 327 (40), 125 (62), 103 (22), 90 (19), 89 (65), 86 (39)
358 (14.5), 343 (38), 342 (24), 341 (100), 127 (29), 125 (70), 91 (25), 90 (20), 89 (64), 86 (30)
372 (35.2), 373 (41.7), 203 (17), 160 (22), 159 (17), 125 (21), 89 (37)
18 mmol), sodium acetate (1.5 g) and glacial acetic acid
(6.0 ml) is heated at 140–150°C for 3 h. After cooling,
the precipitate is filtered, washed with water and recrys-
tallized from methanol. Yield 39%. M.p. 225°C. TLC:
(CHCl3/CH3OH 9:1) Rf 0.66. IR (KBr): w 3240, 1760,
added dropwise to a stirred suspension of 5-(4-bromoben-
zylidene)imidazolidine-2,4-dione (15) (1.3 g, 4.9 mmol) in
50 ml of absolute ethanol. The mixture is refluxed for 2
h. After cooling, the precipitated compound is filtered,
washed with ethanol and dried. A mixture of potassium
salt of the 5-(4-bromobenzylidene)imidazolidine-2,4-
dione (1.2 g, 6.2 mmol) and of 2-chloroacetophenone (0.8
g, 5.2 mmol) in dimethylformamide (50 ml) is refluxed
for 3 h. The precipitated compound is filtered, washed
with minimal quantity of ethanol and purified by column
chromatography with CHCl3/CH3OH (98:2) as eluent.
TLC (CHCl3/CH3OH 98:2): two spots Rf 0.90 and 0.76.
1
1705, 1655 cm−1. H NMR (DMSO-d6): l 4.64 (s, 2H,
CH2); 6.55 (s, 1H, CHꢀ); 7.16 (t, 2H, J=8.7 Hz, aromatic
H); 7.23 (t, 2H, J=8.7 Hz, aromatic H); 7.27–7.30 (m,
2H, aromatic H); 7.67–7.75 (m, 2H, aromatic H). MS:
m/z (%)=314 (57.2), 315 (11.0), 109 (100), 108 (9.0).
3.4. 3-Benzyl- and 3-(4-chlorobenzyl)-4-thioxo-5-
arylideneimidazolidine-2-ones (8–14)
3.6.1. Compound 16
Yield 25%. TLC: (CHCl3/CH3OH 96:4) Rf 0.77. M.p.
An equimolar mixture of 3-benzyl-4-thioxoimidazo-
lidine-2-one (5) (0.51 g, 2.5 mmol) or 3-(4-chlorobenzyl)-
4-thioxoimidazolidine-2-one (6) (0.24 g, 1 mmol),
aldehyde, sodium acetate and glacial acetic acid is heated
at 110–120°C for the time reported in Table 1. After
cooling, theprecipitatedproductiswashedwithwaterand
diethyl ether. Some 3-benzyl-and 3-(4-chlorobenzyl)-4-
thioxo-5-benzylideneimidazolidine-2-ones did not need
another purification. Some compounds were purified by
column chromatography as specified in Table 1.
305–306°C. IR (KBr): w 3230, 2930, 1765, 1710, 1690,
1
1585 cm−1. H NMR (DMSO-d6): l 5.13 (s, 2H, CH2);
6.58 (s, 1H, CHꢀ); 7.62 (s, 4H, aromatic H); 7.59–7.73
(m, 3H, aromatic H); 8.07 (d, 2H, J=7.1 Hz, aromatic
H); 11.06 (bs, 1H, NH). MS m/z (%): 384 (10.5), 386 (8.9),
243 (60), 165 (25), 105 (100), 89 (21).
3.6.2. Compound 17
Yield 2%. TLC: (CHCl3/CH3OH 98:2) Rf 0.90. M.p.
193°C. IR (KBr): w 2930, 1775, 1725, 1695, 1600 cm−1
.
3.5. 5-(4-Bromobenzylidene)imidazolidine-2,4-dione (15)
1H NMR (DMSO-d6): l 4.91 (s, 2H, CH2); 5.13 (s, 2H,
CH2); 6.90 (s, 1H, CHꢀC); 7.02 (d, 2H, J=8.5 Hz,
aromatic H); 7.23 (d, 2H, J=8.4 Hz, aromatic H);
7.35–7.65 (m, 8H, aromatic H); 8.02 (dd, 2H, J=6.6 Hz,
aromatic H). 13C NMR (CDCl3): l 45.18 (CH2), 48.33
(CH2), 111.40 (CH), 122.53 (C), 127.48 (2 CH), 128.11
(2 CH), 128.60 (2 CH), 128.86 (2 CH), 129.54 (C), 130.54
(2 CH), 131.23 (C), 131.42 (2 CH), 133.77 (C), 133.95
(CH), 134.09 (CH), 134.17 (C), 155.35 (CO), 162.91 (CO),
190.36 (CO), 191.24 (CO). MS m/z (%): 502 (4.7), 504
(4.6), 318 (5), 208 (6), 129 (9), 105 (100), 77 (27).
A mixture of imidazolidine-2,4-dione (1) (1.0 g, 10
mmol), 4-bromobenzaldehyde (2.2 g, 12 mmol), sodium
acetate (3.3 g) and glacial acetic acid (14 ml) is heated
at 130–140°C for 5 h. After cooling, the precipitated
product is filtered, triturated with water and diethyl ether
then recrystallized from acetic acid. Yield 50%. M.p.
300°C. TLC: (CHCl3/CH3OH 96:4) Rf 0.28. IR (KBr):
w 3270, 3220, 1790, 1735, 1665 cm−1. 1H NMR (DMSO-
d6): l 6.36 (s, 1H, CHꢀC); 7.55 (s, 4H, aromatic H); 10.91
(s, 1H, NH).
3.6. 3-Phenacyl-5-(4-bromobenzylidene)imidazolidine-
2,4-dione (16) and 1,3-diphenacyl-5-(4-bromobenzyli-
dene)imidazolidine-2,4-dione (17)
3.7. 1-Methylimidazolidine-2,4-dione (18)
According to the method described by Miller and
Robson [13], a mixture of N-methylglycine (5.4 g, 60
mmol) and potassium cyanate (4.9 g, 60 mmol) in 20 ml
A potassium hydroxide solution (0.3 g, 5.3 mmol) is