368
Synthesis and In Vivo Evaluation of 5-Chloro-5-benzobarbiturates as New Central Nervous System Depressants
J. Braz. Chem. Soc.
and 429. 1H NMR (DMSO-d6) d 11.38 (1H, s), 11.27 (1H,
s), 8.28 (1H, s), 8.08 (2H, d, J 7.0 Hz) and 7.48 (3H, t, J
5.0 Hz). 13C NMR (DMSO-d6) d 163.3, 161.5, 154.6, 150.1,
133.0, 132.6, 132.3, 128.2 and 119.1.
1692, 1601, 1423, 1370, 1311, 1219, 1061, 943, 798, 758
and 532. 1H NMR (DMSO-d6) d 11.49 (1H, s), 11.27 (1H,
s), 8.29 (1H, s), 7.73 (1H, d, J 5.5 Hz), 7.53 (1H, t, J 5.0
Hz), 7.46 (1H, t, J 5.8 Hz) and 7.35 (1H, d, J 5.8 Hz). 13C
NMR (DMSO-d6) d 162.7, 160.4, 150.3, 149.8, 133.3,
132.3, 130.0, 132.0, 128.9, 126.4 and 121.8.
5-(4-Methoxibenzylidene)-pyrimidine-2,4,6(1H,3H)-trione
3b
The intense yellow precipitate was obtained in 94.8%
yield; mp 265-268 oC. IR (KBr) nmax/cm-1 3207, 3083, 2832,
1735, 1680, 1555, 1680, 1298, 1252, 1166, 1028, 844, 798,
745 and 512. 1H NMR (DMSO-d6) d 11.28 (1H, s), 11.20
(1H, s), 8.37 (2H, d, J 6.0 Hz), 7.07 (2H, d, J 6.0 Hz) and
3.87 (3H, s). 13C NMR (DMSO-d6) d 163.9, 163.4, 162.1,
154.9, 150.5, 137.4, 125.1, 115.5, 113.9 and 55.7.
General procedure for the preparation of the
5-benzybarbituric acids 4a-f
In a 250 mL round bottom flask there were dissolved
2.5 g of the benzylidene barbituric acid in 150 mL of
95% ethanol. The stirred solution was treated with small
consecutive portions of NaBH4 until the formation of
hydrogen gas was not observed. Then the mixture was
refluxed for 30 min. After cooling to room temperature
the reaction mixture was acidified to pH 2 using 6 mol L-1
hydrochloric acid (HCl). Then the ethanol was evaporated
under vacuum and the residue dissolved in water and
extracted three times with ethyl acetate. The organic extract
was treated with anhydrous sodium sulfate, filtered and the
solvent evaporated under vacuum. The solid product was
recrystallized from an appropriate solvent.
5-(3,4-Methyledioxibenzylidene)-pyrimidine-
2,4,6(1H,3H)-trione 3c
The yellow solid was obtained in 92.6% yield; mp
o
265-266 C. IR (KBr) nmax/cm-1 3230, 3093, 2823, 1735,
1670, 1550, 1454, 1250, 1032, 806, 610 and 501. 1H NMR
(DMSO-d6) d 11.32 (1H, s), 11.20 (1H, s), 8.25 (1H, s), 8.20
(1H, s), 7.72 (1H, d, J 5.6 Hz), 7.05 (1H, d, J 6.2 Hz) and
6.18 (2H, s). 13C NMR (DMSO-d6) d 163.8, 162.2, 154.9,
151.8, 147.3, 133.6 126.7, 115.2, 112.4, 108.3 and 102.3.
5-Benzylbarbituric acid 4a
The white solid was recrystallized from acetic acid,
o
5-(2-Ethoxibenzylidene)-pyrimidine-2,4,6(1H,3H)-trione
3d
leading to 75.4% yield; mp 223-226 C. IR (KBR)
n
max/cm-1 3232, 3097, 2850, 1716, 1495, 1442, 1370, 1206,
1
The intense yellow solid was obtained in 92.9% yield;
mp 260-262 oC IR (KBr) nmax/cm-1 3207, 3083, 2832, 1739,
1681, 1552, 1430, 1377, 1304, 1252, 1173, 1127, 1041,
943, 739, 574 and 535. 1H NMR (DMSO-d6) d 11.33 (1H,
s), 11.15 (1H, s), 8.49 (1H, s), 7.96 (1H, d, J 4.5 Hz), 7.48
(1H, t, J 7.0 Hz), 7.09 (1H, d, J 5.8), 6.95 (1H, t, J 6.0),
1054, 850, 798, 739, 699, 640, 508 and 495. H NMR
(DMSO-d6) d 11.17 (2H, s), 7.23 (3H, m, J 4.0 Hz), 7.09
(2H, d, J 3.8 Hz), 3.90 (1H, t, J 5.0 Hz) and 3.25 (3H, d, J
5.5 Hz). 13C NMR (DMSO-d6) d 169.9, 150.5, 137.4, 128.9,
128.3, 126.7 and 49.3.
13
4.13 (2H, q, J 4.5 Hz), 1.35 (3H, t, J 4.5 Hz). C NMR
5-(4-Methoxibenzyl)-barbituric acid 4b
(DMSO-d6) d 163.4, 161.4, 158.3, 150.2, 150.0, 134.0,
132.5, 121.6, 119.3, 118.6, 111.8, 64.0 and 14.5.
The yellow solid was recrystallized from methanol,
leading to 76.9% yield; mp 204-207 C. IR (KBR)
max/cm-1 3230, 2967, 2654, 2575, 1751, 1574, 1515, 1690,
1304, 1252, 1179, 1113, 1041, 837, 798, 751 and 581. 1H
NMR (DMSO-d6) d 11.92 (2H, s), 7.13 (2H, d, J 3.4 Hz),
7.07 (2H, d, J 3.6 Hz), 4.00 (1H, t, J 4.0 Hz), 3.82 (3H, s)
and 3.51 (2H, d, J 3.8 Hz). 13C NMR (DMSO-d6) d 167.1,
154.8, 149.2, 132.3, 131.0, 113.4, 62.5, 56.8 and 42.4.
o
n
5-(4-Chlorobenzylidene)-pyrimidine-2,4,6(1H,3H)-trione
3e
The yellow solid was obtained in 95% yield; mp 296-
298 oC IR (KBr) nmax/cm-1 3012, 2350, 1703, 1673, 1575,
1490, 1413, 1338, 1223, 1091, 1016, 975, 718 and 681.
1H NMR (DMSO-d6) d 11.41 (1H, s), 11.30 (1H, s), 8.22
(1H, s), 8.08 (2H, d, J 8.7 Hz), 7.53 (2H, d, J 8.7 Hz). 13C
NMR (DMSO-d6) d 163.2, 161.6, 152.9, 150.1, 137.0,
135.0, 131.6, 128.1 and 119.7.
5-(3,4-Methylenedioxibenzyl)-barbituric acid 4c
The yellow solid was recrystallized form methanol,
o
leading to 79.5% yield; mp 255-259 C. IR (KBr)
n
max/cm-1 3417, 3222, 3101, 2846, 1708, 1502, 1442, 1351,
5-(2-Chlorophenyl)-methylene-pyrimidine-2,4,6(1H,3H)-
trione 3f
1317, 1242, 1100, 1041, 923, 811, 626 and 501. 1H NMR
(DMSO-d6) d 11.19 (2H, s), 6.78 (1H, d, J 7.5 Hz), 6.60
(1H, s), 6.55 (1H, d, J 7.5 Hz), 5.96 (2H, s), 3.82 (1H, t, J
4.5 Hz) and 3.17 (2H, d, J 4.5 Hz). 13C NMR (DMSO-d6)
The yellow solid was obtained in 96.5% yield; mp
o
242-243 C IR (KBr) nmax/cm-1 3212, 3081, 2836, 1759,