Aminobarbituric Acid-Hydantoin Rearrangement
4.6 Hz, 3H), 4.45 (d, J ) 16.3 Hz, 1H), 4.64 (d, J ) 16.3 Hz,
1H), 6.97-7.38 (m, 10H), 7.77 (q, J ) 4.6 Hz, 1H), 11.38 (s,
1H); 13C NMR δ 26.5, 44.9, 76.1, 126.7, 127.3, 127.9, 128.0,
128.9, 129.0, 134.2, 137.4, 156.5, 165.5, 171.5; EIMS (m/z)29,31
323 (M+, 4), 266 (59), 175 (19), 91 (100).
25.1, 25.5, 25.6, 30.3, 30.7, 53.9, 69.4, 121.2, 121.5, 128. 8,
138.1, 154.9, 164.8, 171.3; EIMS (m/z)29,32 329 (M+, 4), 210
(100), 128 (83).
1-Ben zyl-3-m eth yl-5-m eth ylcar bam oyl-5-ph en ylh ydan -
toin (5c). To a solution of 4l (0.32 g, 1 mmol) in acetone 90%
(45 mL) were added sodium carbonate (0.21 g, 2 mmol) and
methyl iodide (0.57 g, 0.25 mL, 4 mmol). The mixture was
refluxed for 90 min and filtered. The filtrate was evaporated
under reduced pressure. The crude product was recrystallized
from ethanol to give 5c (120 mg, 35%) as colorless crystals:
5-Ethylcarbamoyl-5-phenyl-1-propylhydantoin (4m ): mp
1
148-152 °C; H NMR δ 0.63 (t, J ) 7.4 Hz, 3H), 1.04 (t, J )
7.3 Hz, 3H), 1.07-1.31 (m, 2H), 3.11-3.25 (m, 4H), 7.23-7.46
(m, 5H), 7.86 (t, J ) 5.7 Hz, 1H), 11.25 (s, 1H); 13C NMR δ
11.2, 14.4, 21.2, 34.6, 43.5, 75.8, 127.9, 128.9, 129.0, 134.8,
156.1, 164.9, 171.7; EIMS (m/z)29,33 289 (M+, 1), 218 (100), 176
(24).
1
mp 148-150 °C; H NMR δ 2.45 (d, J ) 4.6 Hz, 3H), 2.98 (s,
3H), 4.49 (d, J ) 16.1 Hz, 1H), 4.72 (d, J ) 16.1 Hz, 1H), 6.99-
7.40 (m, 10H), 7.88 (q, J ) 4.6 Hz, 1H); 13C NMR δ 25.6, 26.7,
45.4, 75.3, 127.1, 127.7, 128.1, 128.4, 129.1, 129.3, 134.2, 137.3,
156.4, 165.4, 170.5; EIMS (m/z)29,31 337 (M+, 1), 280 (100), 189
(25), 91 (35).
1-Benzyl-5-ethylcarbamoyl-5-phenylhydantoin (4n ): mp 132-
133 °C (ethyl acetate/petroleum ether); 1H NMR δ 0.87 (t, J )
7.3 Hz, 3H), 2.90-3.03 (m, 2H), 4.48 (d, J ) 16.2 Hz, 1H), 4.61
(d, J ) 16.2 Hz, 1H), 6.97-7.39 (m, 10H), 7.80 (t, J ) 5.4 Hz,
1H), 11.33 (s, br, 1H); 13C NMR δ 14.1, 34.5, 44.9, 76.1, 126.7,
127.2, 127.9, 128.0, 128.9, 129.0, 134.4, 137.5, 156.6, 164.7,
171.6; EIMS (m/z)29,31 337 (M+, 5), 266 (79), 175 (24), 91 (100).
1-Benzyl-5-phenyl-5-propylcarbamoylhydantoin (4o). The
crude oil was triturated with ethyl acetate/petroleum ether,
and the product was filtered off: mp 102-105 °C (MeOH); 1H
NMR δ 0.75 (t, J ) 7.4 Hz, 3H), 1.29-1.36 (m, 2H), 2.82-2.98
(m, 2H), 4.50 (d, J ) 16.2 Hz, 1H), 4.59 (d, J ) 16.2 Hz, 1H),
6.96-7.40 (m, 10H), 7.78 (t, J ) 5.7 Hz, 1H), 11.38 (s, 1H);
13C NMR δ 11.4, 21.9, 41.3, 44.9, 76.3, 126.7, 127.2, 127.9,
128.1, 128.9, 129.0, 134.4, 137.5, 156.5, 164.9, 171.6; EIMS
(m/z)29,31 351 (M+, 3), 266 (52), 175 (11), 91 (76).
5-Eth ylca r ba m oyl-3-m eth yl-5-p h en yl-1-p r op ylh yd a n -
toin (5d ). To a solution of 4m (0.29 g, 1 mmol) in acetone 90%
(45 mL) were added sodium carbonate (0.21 g, 2 mmol) and
methyl iodide (0.57 g, 0.25 mL, 4 mmol). The mixture was
refluxed for 90 min and filtered. The volume of the solvent
was reduced. After cooling, the precipitate was collected and
recrystallized from EtOH to give 5d (35 mg, 12%) as colorless
1
crystals: mp 68-70 °C; H NMR δ 0.64 (t, J ) 7.4 Hz, 3H),
1.05 (t, J ) 7.3 Hz, 3H), 1.09-1.36 (m, 2H), 2.94 (s, 3H), 3.14-
3.31 (m, 4H), 7.25-7.45 (m, 5H), 7.92 (t, J ) 5.7 Hz, 1H); 13
C
NMR δ 11.1, 14.4, 21.1, 25.2, 34.7, 43.9, 74.8, 128.1, 128.9,
129.1, 134.5, 155.7, 164.6, 170.4; MS (FAB) 304 (MH+); EIMS
(m/z)29,33 232 (100), 190 (11).
5-Phenyl-5-phenylcarbamoyl-1-propylhydantoin (4p ): mp
1
75-79 °C; H NMR δ 0.63 (t, J ) 7.4 Hz, 3H), 1.12-1.19 (m,
3-E t h yl-5-e t h ylca r b a m oyl-5-p h e n yl-1-p r op ylh yd a n -
toin (5e). To a solution of 4m (0.89 g, 3 mmol) in acetone 90%
(135 mL) were added sodium carbonate (0.96 g, 9 mmol) and
ethyl bromide (1.96 g, 1.34 mL, 18 mmol). The mixture was
refluxed for 3 h and filtered. The filtrate was evaporated to
dryness. The crude product was purified by column chroma-
tography (eluent, 5:3 methanol/hexane) to give 5e (156 mg,
1H), 1.25-1.34 (m, 1H), 3.21-3.35 (m, 2H), 7.11-7.60 (m,
10H), 9.69 (s, 1H), 11.38 (s, 1H); 13C NMR δ 11.2, 21.2, 43.4,
76.7, 121.4, 124.8, 128.0, 128.7, 129.1, 129.2, 134.5, 137.8,
156.1, 164.2, 171.3; MS (FAB) 338 (MH+); EIMS (m/z)29,33 218
(100), 176 (10).
1-Isopropyl-5-phenyl-5-phenylcarbamoylhydantoin (4r ): mp
172-174 °C; 1H NMR δ 0.91, (d, J ) 6.9 Hz, 3H), 1.41 (d, J )
6.9 Hz, 3H), 3.50 (sept., J ) 6.9 Hz, 1H), 7.11-7.62 (m, 10H),
9.54 (s, 1H), 11.37 (s, 1H); 13C NMR δ 20.0, 20.3, 46.8, 77.3,
121.2, 124.7, 128.2, 128.8, 129.1, 129.4, 134.8, 137.7, 154.8,
163.9, 171.7; EIMS (m/z)29,30 337 (M+, 2), 218 (100), 176 (43).
1-Benzyl-5-phenyl-5-phenylcarbamoylhydantoin (4s): mp
185-195 °C (EtOH/diethyl ether/cyclohexane); 1H NMR δ 4.39
(d, J ) 16.0 Hz, 1H), 4.56 (d, J ) 16.0 Hz, 1H), 7.02-7.46 (m,
15H), 10.21 (s, 1H). One NH signal did not appear. 13C NMR
δ 45.3, 76.3, 120.3, 124.2, 125.1, 127.4, 127.6, 127.6, 128.3,
128.8, 128.8, 136.9, 137.8, 139.3, 165.6. Two carbonyl signals
did not appear. MS (FAB) 386 (MH+); EIMS (m/z)29,31 385 (M+,
2), 266 (97), 175 (17), 91 (100).
1-Ben zyl-3,5-dim eth yl-5-eth ylcar bam oylh ydan toin (5a).
To a solution of 4f (0.29 g, 1 mmol) in acetone 90% (45 mL)
were added sodium carbonate (0.21 g, 2 mmol) and methyl
iodide (0.57 g, 0.25 mL, 4 mmol). The mixture was refluxed
for 90 min and filtered. The filtrate was evaporated under
reduced pressure. The crude product was purified by column
chromatography (eluent, 2:1 ethyl acetate/petroleum ether) to
give 5a as a colorless oil (60 mg, 21%): 1H NMR δ 0.88 (t, J )
7.2 Hz, 3H), 1.37 (s, 3H), 2.91 (s, 3H), 2.92-2.98 (m, 2H), 4.22
(d, J ) 16.1 Hz, 1H), 4.59 (d, J ) 16.1 Hz, 1H), 7.21-7.31 (m,
5H), 7.98 (t, J ) 5.4 Hz, 1H); 13C NMR δ 14.3, 18.5, 25.2, 34.4,
44.2, 68.6, 127.4, 128.0, 128.3, 137.4, 156.5, 164.9, 171.7; EIMS
(m/z)29,31 289 (M+, 1), 218 (100), 127 (75), 91 (100).
1
16%) as a white solid: mp 86-88 °C; H NMR δ 0.63 (t, J )
7.4 Hz, 3H), 1.03 (t, J ) 7.3 Hz, 3H), 1.10 (t, J ) 7.3 Hz, 3H),
1.10-1.34 (m, 2H), 3.14-3.27 (m, 4H), 3.45-3.51 (m, 2H),
7.22-7.46 (m, 5H), 7.90 (t, J ) 5.7 Hz, 1H); 13C NMR δ 11.1,
13.2, 14.4, 21.1, 33.9, 34.6, 43.8, 74.7, 128.0, 129.0, 129.2, 134.5,
155.4, 164.6, 170.1; MS (FAB) 318 (MH+); EIMS (m/z)29,33 246
(100), 204 (5).
3-Meth yl-5-p h en yl-5-p h en ylca r ba m oyl-1-p r op ylh yd a n -
toin (5f). To a solution of 4p (0.34 g, 1 mmol) in acetone 90%
(45 mL) were added sodium carbonate (0.21 g, 2 mmol) and
methyl iodide (0.57 g, 0.25 mL, 4 mmol). The mixture was
refluxed for 90 min and filtered. The volume of the solvent
was reduced. After cooling, the precipitate was collected by
suction filtration to give 5f (340 mg, 94%) as colorless
crystals: mp 160-163 °C; 1H NMR δ 0.67 (t, J ) 7.4 Hz, 3H),
1.16-1.19 (m, 1H), 1.25-1.33 (m, 1H), 3.00 (s, 3H), 3.27-3.31
(m, 1H), 3.38-3.44 (m, 1H), 7.14-7.62 (m, 10H), 9.75 (s, 1H);
13C NMR δ 11.2, 21.2, 25.4, 43.8, 75.6, 121.3, 124.8, 128.2,
128.8, 129.0, 129.3, 134.2, 137.8, 155.8, 163.9, 170.1; EIMS
(m/z)29,33 351 (M+, 1), 232 (100), 190 (7).
3-Eth yl-5-p h en yl-5-p h en ylca r ba m oyl-1-p r op ylh yd a n -
toin (5g). To a solution of 4p (1.01 g, 3 mmol) in acetone 90%
(135 mL) were added sodium carbonate (0.96 g, 9 mmol) and
ethyl bromide (1.96 g, 1.34 mL, 18 mmol). The mixture was
refluxed for 3 h and filtered. The volume of the filtrate was
reduced and cooled. The precipitate was filtered off and
recrystallized from EtOH to give 5g (781 mg, 71%) as colorless
needles: mp 155-158 °C; 1H NMR δ 0.63 (t, J ) 7.3 Hz, 3H),
1.12 (t, J ) 7.3 Hz, 3H), 1.08-1.19 (m, 1H), 1.24-1.33 (m, 1H),
3.27-3.39 (m, 2H), 3.48-3.57 (m, 2H), 7.11-7.60 (m, 10H),
9.75 (s, 1H); 13C NMR δ 11.2, 13.2, 21.2, 34.1, 43.7, 75.5, 121.4,
124.8, 128.1, 128.8, 129.2, 129.4, 134.2, 137.8, 155.4, 163.9,
169.8; EIMS (m/z)29,33 365 (M+, 1), 246 (100), 204 (15).
1-Cycloh exyl-3,5-d im eth yl-5-p h en ylca r ba m oylh yd a n -
toin (5b). To a solution of 4i (0.32 g, 1 mmol) in acetone 90%
(45 mL) were added sodium carbonate (0.21 g, 2 mmol) and
methyl iodide (0.57 g, 0.25 mL, 4 mmol). The mixture was
refluxed for 90 min and filtered. The filtrate was evaporated
under reduced pressure. The crude product was recrystallized
from ethanol to give 5b (184 mg, 55%) as colorless crystals:
mp 140-141 °C; 1H NMR δ 1.03-2.03 (m, 10H), 1.64 (s, 3H),
2.88 (s, 3H), 3.13-3.20 (m, 1H), 7.08-7.13 (m, 1H), 7.29-7.35
(m, 2H), 7.51-7.57 (m, 2H), 9.76 (s, 1H); 13C NMR δ 19.5, 25.0,
1-Ben zyl-3-m eth yl-5-ph en yl-5-ph en ylcar bam oylh ydan -
toin (5h ). To a solution of 4s (0.41 g, 1 mmol) in acetone 90%
(45 mL) were added sodium carbonate (0.21 g, 2 mmol) and
J . Org. Chem, Vol. 68, No. 12, 2003 4691