Jul-Aug 2004
Cyclocondensation Reaction of Heterocyclic Carbonyl Compounds
599
3-[2-(2-Oximinoacetylamino)phenyl]-1,2-dihydro-quinoxalin-2-
one (2).
11.96 (s, 1H, NH), 12.35 (s, 1H, NH), 12.50 (s, 1H, NH); ms: m/z
+
349 [M+H] .
Anal. Calcd. for C H N O (348.32): C, 58.62; H, 3.47; N,
17 12
6 3
24.13. Found: C, 59.01; H, 3.42; N, 24.22.
To the solution of 3-(2-aminophenyl)-1,2-dihydro-quinoxalin-
2-one (1) [3] (15.00 g, 63 mmoles) in a boiling mixture of water
(2400 ml) and 37% HCl (45 ml) was added chloralhydrate (12.00
g, 72,6 mmoles) in water (20 ml). After 1 minute a solution of
hydroxylamine hydrochloride (16.20 g, 234.8 mmoles) in water
(20 ml) was added and the reaction mixture was refluxed for 25
minutes. The next day the solid was collected by filtration,
washed with water and dried to yield 13.40 g (69%), mp 260-
6 - ( 3 - O x o - 3 , 4 - d i h y d r o - q u i n o x a l i n - 2 - y l ) - 4 H- 2 , 3 - d i h y d r o -
[1,2,4]triazino[5,6-b]indol-3-one (6).
Compound (5) (100.0 mg, 0.29 mmoles) was refluxed in acetic
acid (15 ml) for 5 hours. Then the solvent was evaporated with
heating to one third of volume and cooled. The yellow crystalline
solid was collected by filtration, washed with water and dried to
yield 80.0 mg (95%), mp >360°; ir: NH 3285, Ar-H 3007, CO
-1 1
262°; ir: NH 3282, Ar-H 3003, CO 1669 cm ; H nmr: δ 7.26 (t,
1H, Ar-H, J= 7.5 Hz), 7.38 (m, 2H, Ar-H), 7.55 (m, 3H, Ar-H, C-
H), 7.91 (d, 1H, Ar-H, J= 7 Hz), 8.14 (m, 2H, Ar-H), 11.29 (s,
1H, NH), 12.29 (s, 1H, NH), 12.68 (b, 1H, =NOH); ms: m/z 309
-1 1
1686, 1658 cm ; H nmr: δ 7.37 (m, 3H, Ar-H), 7.60 (t, 1H, Ar-
H, J= 7 Hz), 8.00 (m, 2H, Ar-H), 8.18 (d, 1H, Ar-H, J= 7 Hz),
11.85 (b, 1H, NH), 12.70 (b, 1H, NH), 13.05 (b, 1H, NH); ms:
+
[M+H] .
+
m/z 331 [M+H] . Fragments obtained by collision-induced dis-
Anal. Calcd. for C H N O (308.30): C, 62.34; H, 3.92; N,
16 12 4 3
18.17. Found: C, 61.94; H, 3.88; N, 17.77.
sociation of the quasimolecular ions had massed: 313 (11), 303
(100), 286 (25), 275 (56), 260 (12), 248 (51), 245(26).
Anal. Calcd. for C H N O (330.31): C, 61.82; H, 3.05; N,
3-(2,3-Dioxo-2,3-dihydro-indole-7-yl)-2,3-dihydro-quinoxalin-
2-one (3).
17 10 6 2
25.44. Found: C, 61.65; H, 3.01; N, 24.98.
Compound (2) (13.39 g, 43.4 mmoles) was added to 89% sul-
furic acid (145 ml). The mixture was stirred at 55-60° for 7 hours.
Then the mixture was poured onto crushed ice. The next day, the
resulting solid was collected by filtration, properly washed with
water and dried at 150° to yield 7.00 g (55%). Recrystallization
from N,N-dimethylformamide afforded orange crystals, mp
>360°; ir: NH 3320, CO 1743, 1656 cm ; H nmr: δ 7.20 (t, 1H,
Ar-H, J= 7.5 Hz), 7.38 (m, 2H, Ar-H), 7.63 (m, 2H, Ar-H), 7.93
(d, 1H, Ar-H, J= 7.5 Hz), 8.18 (d, 1H, Ar-H, J= 7.5 Hz), 10.89 (b,
4 - ( 3 , 5 - D i o x o - 2 , 3 , 4 , 5 - t e t r a h y d r o [ 1 , 2 , 4 ] t r i a z i n - 6 - y l ) - 5 H-
indolo[2,3-b]quinoxaline (7).
To the mixture of compound (8) (200.0 mg, 0.78 mmoles) [4]
in N,N-dimethylformamide (10 ml) o-phenylendiamine (84.0 mg,
0.78 mmoles) was added and the reaction mixture was refluxed
for 30 minutes. After cooling, the yellow crystalline solid was
collected by filtration, washed with ethanol, water and dried to
yield 150.0 mg (58.5%), mp >360°; ir: NH 3296, 2982, CO 1716,
-1 1
-1
1684 cm ; 1H nmr: δ 7.45 (t, 1H, Ar-H, J= 8 Hz), 7.79 (m, 2H,
+
1H, NH), 12.58 (b, 1H, NH); ms: m/z 292 [M+H] .
Anal. Calcd. for C H N O (291.27): C, 65.98; H, 3.11; N,
Ar-H), 7.94 (d, 1H, Ar-H, J= 7 Hz), 8.10 (d, 1H, Ar-H, J= 7 Hz),
8.29 (d, 1H, Ar-H, J= 8 Hz), 8.45 (d, 1H, Ar-H, J= 7 Hz), 11.85
(s, 1H, NH), 12.27 (b, 1H, NH), 12,49 (b, 1H, NH); ms: m/z
16
14.43. Found: C, 65.70; H, 2.98; N, 13.97.
9 3 3
+
3-(2-Oxo-3-carbamoylhydrazono-2,3-dihydro-indol-7-yl)-2,3-
dihydro-quinoxaline-2-one (4).
331[M+H] . Fragments obtained by collision-induced dissocia-
tion of the quasimolecular ions had masses: 303 (2), 292 (3), 260
(100), 245 (3), 232(10).
Anal. Calcd. for C H N O (330.31): C, 61.82; H, 3.05; N,
To the boiling solution of compound (3) (500.0 mg, 1.7
mmoles) in acetic acid
17 10
6 2
25.44. Found: C, 61.75; H, 3.04; N, 25.05.
(300 ml) semicarbazide hydrochloride (300.0 mg, 2.7 mmoles)
was added. The reaction mixture was refluxed for 5 hours. Then
the solvent was evaporated to dryness, the solid was then mixed
with water (100 ml), collected by filtration and dried to yield
320.0 mg (53.5%), mp >360°; ir: NH 3497, 3230, Ar-H 3009, CO
Acknowledgements.
Financial support for this work by the Ministry of Education,
Youth and Sport of Czech Republic, grant No 15 31 0008 and 15
31 00013, is gratefully acknowledged.
-1 1
1740, 1698, 1664 cm ; H nmr: δ 7.20 (m, 3H, Ar-H, NH ), 7.35
2
(m, 2H, Ar-H), 7.57 (t, 1H, Ar-H, J= 7.7 Hz), 7.76 (d, 1H, Ar-H,
J= 7.5), 7.95 (m, 2H, Ar-H), 10.91 (b, 1H, NH), 11.75 (b, 1H,
REFERENCES AND NOTES
+
NH), 12.54 (b, 1H, NH). ms: m/z 349 [M+H] .
Anal. Calcd. for C H N O (348.32): C, 58.62; H, 3.47; N,
17 12
24.13. Found: C, 57.98; H, 3.40; N, 23.89.
6 3
[1] Part 10 in this series. For the previous paper see: P. Bílek
and J. Slouka, Heterocycl. Commun. 10, 67 (2004)
[2] J. Hlavácˇ, J. Slouka, P. Hradil and K. Lemr, J. Heterocyclic
Chem. 37, 115 (2000).
3-[2-Amino-3-(3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-
yl)phenyl]-2,3-dihydro-quinoxalin-2-one (5).
[3] E. Schunck and L. Marchlewski, Ber. Dtsch. Chem. Ges.
29, 194 (1896); I. Wiedermannová, J. Slouka and J. Hlavácˇ, Acta
Univ. Palacki. Olomouc., Fac. Rerum Nat., Chemica 39, 69 (2000);
Chem. Abstr. 136, 134 733b (2002).
[4] J. Hlavácˇ and J. Slouka, J. Heterocyclic Chem. 3 4, 917
(1997).
[5] J. Bergman, C. Staalhandske and H. Vallberg, Acta
Chemica Scandinavica 51(6/7), 753 (1997).
[6] A. A. Samarkandy, S. Al-Thabaiti, E. A. Hamed and I. M.
Sidahmed, Alexandria Journal of Pharmaceutical Sciences, 10, 161
(1996).
Compound (4) (100.0 mg, 0.29 mmoles) was refluxed in 10%
solution of sodium bicarbonate (20 ml) for 4.5 hours. After cool-
ing, the mixture was filtered then acidified with acetic acid. The
resulting powder was collected by filtration after several hours,
washed with water and dried at 100° to yield 83.0 mg (83%).
Recrystallization from cellosolve afforded yellow crystals, mp
-
>360°; ir: NH 3382, 3251, Ar-H 3041, CO 1730, 1705, 1648 cm
1 1
; H nmr: δ 6.32 (s, 2H, NH ), 6.65 (t, 1H, Ar-H, J= 8 Hz), 7.23
2
(d, 1H, Ar-H, J= 6 Hz), 7.32 (m, 2H, Ar-H), 7.53 (t, 1H, Ar-H, J=
8 Hz), 7.78 (d, 1H, Ar-H, J= 8 Hz), 7.95 (d, 1H, Ar-H, J= 6 Hz),