T. Hosoya et al. / Bioorg. Med. Chem. 11 (2003) 663–673
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4.33 (s, 2H), 6.97–6.99 (m, 2H), 7.63 (t, 1H, J=7.8 Hz),
7.67 (s, 1H), 7.78 (t, 1H, J=7.8 Hz), 7.87 (d, 1H,
J=7.8 Hz), 7.96 (d, 1H, J=7.8 Hz), 11.28 (s, 1H); 13C
NMR (100 MHz, DMSO-d6) d 48.9, 112.1, 114.5, 122.6,
124.3, 129.5, 129.9, 132.5, 132.9, 147.0, 149.3, 150.8,
153.2, 168.9; IR (KBr, cmꢀ1) 743, 808, 818, 1125, 1213,
1347, 1385, 1437, 1522, 1538, 1732, 1786. Anal. calcd
for C14H10N4O5: C, 53.51; H, 3.21; N, 17.83. Found: C,
53.24; H, 3.55; N, 17.67.
DMSO-d6) d 4.34 (s, 2H), 6.95(d, 1H, J=3.4 Hz), 7.10
(d, 1H, J=3.4 Hz), 7.27–7.34 (AA0BB0 with H–F cou-
pling, 2H), 7.71 (s, 1H), 7.78–7.84 (AA0BB0 with H–F
coupling, 2H), 11.27 (s, 1H); 13C NMR (100 MHz,
DMSO-d6)
d 48.9, 108.1, 115.4, 116.1 (d, 2C,
2JCꢀF=22.3 Hz,), 126.1 (d, 2C, 3JCꢀF=8.3 Hz), 126.2 (d,
4JCꢀF=3.3 Hz), 133.0, 149.2, 153.3, 153.5, 161.9 (d,
1JCꢀF=245.6 Hz), 168.9; 19F NMR (372 MHz, DMSO-
3
4
d6) d ꢀ34.7 (tt, 1F, JFꢀH=9.2, JFꢀH=5.3 Hz); IR
(KBr, cmꢀ1) 426, 612, 741, 791, 851, 924, 978, 1115,
1127, 1228, 1352, 1410, 1435, 1455, 1493, 1719, 1775,
1808. Anal. calcd for C14H10N3O3F: C, 58.54; H, 3.51;
N, 14.63. Found: C, 58.42; H, 3.63; N, 14.51.
1-{[5-(2-Nitrophenyl)furfurylidene]amino}imidazolidine-
2,4-dione (9h). ꢁYellow solid (ethanol); mp 224–226 ꢁC
1
(lit.9a 224–226 C); H NMR (400 MHz, DMSO-d6) d
4.33 (s, 2H), 6.97–6.99 (m, 2H), 7.63 (t, 1H, J=7.8 Hz),
7.67 (s, 1H), 7.78 (t, 1H, J=7.8 Hz), 7.87 (d, 1H,
J=7.8 Hz), 7.96 (d, 1H, J=7.8 Hz), 11.28 (s, 1H); 13C
NMR (100 MHz, DMSO-d6) d 48.9, 112.1, 114.5, 122.6,
124.3, 129.5, 129.9, 132.5, 132.9, 147.0, 149.3, 150.8,
153.2, 168.9; IR (KBr, cmꢀ1) 608, 696, 746, 787, 926,
980, 1022, 1136, 1210, 1244, 1348, 1402, 1437, 1464,
1518, 1701, 1755, 1803, 3071. Anal. calcd for
C14H10N4O5: C, 53.51; H, 3.21; N, 17.83. Found: C,
53.42; H, 3.31; N, 17.65.
1-{[5-(4-Phenylphenyl)furfurylidene]amino}imidazolidine-
2,4-dione (9l). Yellow solid (ethanol–DMF); mp 276–
278 ꢁC; 1H NMR (400 MHz, DMSO-d6) d 4.35(s,
2H), 6.98 (d, 1H, J=3.6 Hz), 7.18 (d, 1H, J=3.6 Hz),
7.38 (tt, 1H, J=1.2, 7.5Hz), 7.48 (ddd, 2H, J=1.9,
7.3, 7.5Hz), 7.71 (ddd, 2H, J=1.2, 1.9, 7.3 Hz), 7.74
(s, 1H), 7.75–7.80 (AA0BB0, 2H), 7.84–7.88 (AA0BB0,
2H), 11.25(s, 1H); 13C NMR (100 MHz, DMSO-d6)
d 49.1, 108.6, 115.5, 124.4 (2C), 126.5 (2C), 127.2
(2C), 127.7, 128.5, 129.0 (2C), 133.0, 139.2, 139.6,
149.2, 153.2, 154.0, 168.8; IR (KBr, cmꢀ1) 600, 687,
762, 795, 839, 1117, 1213, 1228, 1348, 1397, 1447,
1472, 1732, 1767, 1777. Anal. calcd for C20H15N3O3:
C, 69.56; H, 4.38; N, 12.17. Found: C, 69.43; H, 4.31;
N, 12.06.
1-{[5-(4-Trifluoromethylphenyl)furfurylidene]amino}imi-
dazolidine-2,4-dione (9i). Light yellow solid (ethanol);
mp 254 ꢁC (sublim); H NMR (400 MHz, DMSO-d6) d
1
4.35(s, 2H), 7.01 (d, 1H, J=3.7 Hz), 7.34 (d, 1H,
J=3.7 Hz), 7.75(s, 1H), 7.82 (d, 2H, J=8.3 Hz), 7.98
(d, 2H, J=8.3 Hz), 11.30 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) d 49.1, 110.6, 115.3, 124.1 (q,
1JCꢀF=271.5Hz), 124.3 (2C), 125.9 (q, 2C,
1-{[5-(2,6-Dinitrophenyl)furfurylidene]amino}imidazolidine-
2,4-dione (9m). Yellow solid (ethanol); mp 287–290 ꢁC
2
1
3JCꢀF=3.3 Hz), 127.8 (q, JCꢀF=31.3 Hz), 132.7, 133.0,
(decomp); H NMR (400 MHz, DMSO-d6) d 4.32 (s,
150.1, 152.5, 153.2, 168.7; 19F NMR (372 MHz, DMSO-
d6) d 17.30 (s, 3F); IR (KBr, cmꢀ1) 602, 795, 843, 1075,
1111, 1123, 1148, 1179, 1190, 1221, 1333, 1447, 1717,
1730, 1777. Anal. calcd for C15H10N3O3F3: C, 53.42; H,
2.99; N, 12.46. Found: C, 53.66; H, 3.31; N, 12.48.
2H), 6.84 (d, 1H, J=3.7 Hz), 6.96 (d, 1H, J=3.7 Hz),
7.67 (s, 1H), 8.01 (t, 1H, J=8.1 Hz), 8.43 (d, 2H,
J=8.1 Hz), 11.26 (s, 1H); 13C NMR (100 MHz, DMSO-
d6) d 48.9, 114.1, 114.6, 117.7, 128.3 (2C), 132.3, 132.5,
142.7, 149.3 (2C), 151.5, 153.2, 168.9; IR (KBr, cmꢀ1
)
440, 608, 693, 708, 731, 752, 797, 826, 876, 899, 927,
978, 1018, 1132, 1213, 1254, 1353, 1360, 1402, 1433,
1538, 1732, 1788, 3083. Anal. calcd for C14H9N5O7: C,
46.81; H, 2.53; N, 19.49. Found: C, 46.86; H, 2.64; N,
19.22. Synthesis of 9m sodium salt: To a solution of 9m
(470 mg, 1.31 mmol) in methanol (20 mL) was added
sodium methoxide (580 mM methanol solution,
2.50 mL, 1.44 mmol) and the mixture was stirred for 8 h
at room temperature. The solvent was removed under
reduced pressure and the crude product was washed
successively with acetone (5mL ꢄ 5), ether (5 mL ꢄ 2),
and hexane (5mL ꢄ 2). The resulting solid was dis-
solved with water (100 mL), filtered to remove in-
solubles, and lyophilized to give sodium salt of 9m
1-{[5-(2,3,4,5,6-Pentafluorophenyl)furfurylidene]amino}-
imidazolidine-2,4-dione (9j). Light yellow solid (etha-
nol); mp 220 C (sublim); H NMR (400 MHz, DMSO-
ꢁ
1
d6) d 4.34 (s, 2H), 7.07 (d, 1H, J=3.7 Hz), 7.13
3
5
(dHꢀH HꢀF, 1H, JHꢀH=3.7, JHꢀF=3.7 Hz), 7.75(s,
t
1H), 11.31 (s, 1H); 13C NMR (100 MHz, DMSO-d6) d
49.1, 105.7 (dd, 2JCꢀF=14.8, 3JCꢀF=4.9Hz), 114.0, 116.1
(dd, 3JCꢀF=1.6, 4JCꢀF=4.9 Hz), 132.3, 137.5(ddd, JCꢀF
1
2
3
=248.4, JCꢀF=13.2, JCꢀF=3.3 Hz), 139.9 (ddddd,
1
2
3
3
2C, JCꢀF=251.7, JCꢀF=14.8, JCꢀF=4.9, JCꢀF=3.3,
4JCꢀF=9.3 Hz), 140.9 (d, JCꢀF=3.3 Hz), 143.0 (ddddd,
3
1
2
2
3
2C, JCꢀF=255.0, JCꢀF=11.5, JCꢀF= 11.5, JCꢀF
=
3.3, JCꢀF=8.2 Hz), 151.0, 153.1, 168.6; 19F NMR
4
(372 MHz, DMSO-d6) d ꢀ83.88 (ddd, 2F, JFꢀF=22.1,
(484 mg, 86.7%); yellow solid; mp 251 ꢁC (decomp); H
3
1
3JFꢀF=22.1, JFꢀF=6.1 Hz), ꢀ76.64 (t, 1F, JFꢀF
=
NMR (400 MHz, DMSO-d6) d 3.64 (s, 2H), 6.72 (d, 1H,
J=3.4 Hz), 6.76 (d, 1H, J=3.4 Hz), 7.32 (s, 1H), 7.95(t,
1H, J=8.0 Hz), 8.38 (d, 2H, J=8.0 Hz); 13C NMR
(100 MHz, DMSO-d6) d 49.5, 111.3, 114.2, 117.7, 126.8,
128.1 (2C), 132.1, 141.2, 149.2 (2C), 153.4, 166.3, 180.4;
IR (KBr, cmꢀ1) 627, 708, 750, 779, 797, 823, 835, 878,
914, 976, 1021, 1161, 1223, 1256, 1364, 1435, 1538,
4
3
22.1 Hz), ꢀ62.70 (dd, 2F, 3JFꢀF=22.1, 4JFꢀF=6.1Hz); IR
(KBr, cmꢀ1) 444, 612, 745, 789, 818, 903, 978, 1005, 1084,
1127, 1213, 1244, 1356, 1385, 1435, 1495, 1510, 1532,
1728, 1782. Anal. calcd for C14H6N3O3F5: C, 46.81; H,
1.68; N, 11.70. Found: C, 46.85; H, 1.92; N, 11.67.
.
1-{[5-(4-Fluorophenyl)furfurylidene]amino}imidazolidine-
2,4-dione (9k). Light yellow solid (ethanol); mp 261 ꢁC
(sublim) (lit.9a 264–265 ꢁC); 1H NMR (400 MHz,
1603, 1716, 3085. Anal. calcd for C14H8N5O7 2.5H2O:
C, 39.45; H, 3.07; N, 16.43. Found: C, 39.40; H, 2.74; N,
16.16.