´
R. Chicharro, S. de Castro, J. L. Reino, V. J. Aran
FULL PAPER
6-, 8-H), 6.75 (d, J ϭ 9.1 Hz, 1 H, 5-H), 4.21 (s, 2 H, 3-H), 2.93 10-HB), 2.06Ϫ1.34 (m, 6 H, 7-, 8-, 9-H) ppm. 13C NMR
(s, 3 H, CH3) ppm.
([D6]DMSO): δ ϭ 166.2 (C-6), 140.3 (C-11a), 137.5 (C-3), 126.0
(C-4a), 120.2 (C-2), 110.3 (C-1), 109.5 (C-4), 59.1 (C-6a), 46.0 (C-
10), 27.7 (C-7), 23.3, 22.9 (C-8, -9) ppm. EI MS: m/z (%) ϭ 247
(83) [Mϩ], 218 (100), 200 (7), 190 (28), 172 (17), 163 (58), 144 (10),
133 (16), 117 (16), 105 (5), 90 (9). C12H13N3O3 (247.25): calcd. C
58.29, H 5.30, N 16.99; found C 58.36, H 5.50, N 17.09.
(S)-5-Hydroxy-7-nitro-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a]quin-
oxalin-4-one (27): 1H NMR ([D6]DMSO): δ ϭ 10.92 (br. s, 1 H,
OH), 7.90 (dd, J ϭ 8.8, 2.6 Hz, 1 H, 8-H), 7.82 (d, J ϭ 2.6 Hz, 1
H, 6-H), 6.65 (d, J ϭ 8.8 Hz, 1 H, 9-H), 4.33 (m, 1 H, 3a-H), 3.45
(m, 2 H, 1-H), 2.26 (m, 1 H, 3-HA), 2.00 (m, 3 H, 2-H, 3-HB) ppm.
EI MS: m/z (%) ϭ 249 (50) [Mϩ], 232 (91), 204 (84), 186 (62), 177
(61), 158 (100), 130 (27), 118 (12), 117 (12), 103 (15), 89 (13).
3-Nitro-6a,7-dihydro-5H-indolo[1,2-a]quinoxalin-6-one (37): Yield:
0.17 g (6%) (Method b); crystals of compound 37 (pyridine/water)
decompose without melting above ca. 220 °C affording a copious
sublimate of thin needles that was shown to be (TLC) dehydro
derivative 56 (m.p. Ͼ 360 °C, see below). IR (nujol): ν˜ ϭ 1682 (CO)
5-Hydroxy-3-nitro-7,8,9,10-tetrahydro-5H,6aH-pyrido[1,2-a]-
quinoxalin-6-one (28): 1H NMR ([D6]DMSO): δ ϭ 11.01 (br. s, 1
H, OH), 7.88 (m, 2 H, 2-, 4-H), 7.00 (d, J ϭ 9.0 Hz, 1 H, 1-H),
4.16 (m, 1 H, 6a-H), 3.98 (br. d, J ϭ (Ϫ)13 Hz, 1 H, 10-HA), 2.94
(br. dd, J ϭ (Ϫ)13, 13 Hz, 1 H, 10-HB), 2.10Ϫ1.40 (m, 6 H, 7-, 8-
, 9-H) ppm. EI MS: m/z (%) ϭ 263 (33) [Mϩ], 246 (100), 218 (77),
200 (42), 190 (14), 172 (67), 163 (28), 144 (14), 133 (13), 117 (20),
105 (15), 97 (12), 90 (13).
cmϪ1 1H NMR ([D6]DMSO): δ ϭ 11.05 (br. s, 1 H, NH), 7.91
.
(dd, J ϭ 9.0, 2.7 Hz, 1 H, 2-H), 7.80 (d, J ϭ 2.7 Hz, 1 H, 4-H),
7.70 (d, J ϭ 9.0 Hz, 1 H, 1-H), 7.33 (d, J ϭ 7.5 Hz, 1 H, 11-H),
7.26 (d, J ϭ 7.5 Hz, 1 H, 8-H), 7.17 (dd, J ϭ 7.5, 7.5 Hz, 1 H, 10-
H), 6.93 (dd, J ϭ 7.5, 7.5 Hz, 1 H, 9-H), 4.78 (dd, J ϭ 10.8, 9.3 Hz,
1 H, 6a-H), 3.44 (dd, J ϭ (Ϫ)16.8, 9.3 Hz, 1 H, 7-HA), 3.39 (dd,
J ϭ (Ϫ)16.8, 10.8 Hz, 1 H, 7-HB) ppm. 13C NMR ([D6]DMSO):
δ ϭ 167.9 (C-6), 144.3 (C-11a), 141.1 (C-3), 136.0 (C-12a), 130.3
(C-4a), 130.0 (C-7a), 128.4 (C-10), 126.2 (C-8), 122.4 (C-9), 119.9
(C-2), 116.4 (C-1), 111.4 (C-4), 109.8 (C-11), 60.3 (C-6a), 30.2 (C-
7) ppm. EI MS: m/z (%) ϭ 281 (85) [Mϩ], 265 (3), 252 (100), 235
(7), 222 (11), 206 (52), 191 (6), 180 (11), 178 (13), 167 (4), 152 (6),
140 (4), 128 (5), 117 (8), 103 (9), 89 (17). C15H11N3O3 (281.3):
calcd. C 64.05, H 3.94, N 14.94; found C 64.18, H 3.81, N 14.67.
Quinoxalinones 33؊38: These compounds were prepared from
DNP-imino acids 7Ϫ12 following Methods a1 and/or b and, in the
case of quinoxalinone 34, also from DNP--proline methyl ester 13
following Methods c1 and c2.
4-Methyl-7-nitro-3,4-dihydro-1H-quinoxalin-2-one
(33):
Yield:
63 mg (10%) (Method a1), 1.35 g (65%) (Method b); m.p. 262Ϫ264
°C (decomp., pyridine/water), ref.[5] m.p. 262Ϫ264 °C.
3-Nitro-6a,7-dihydro-5H,12H-isoquinolino[2,3-a]quinoxalin-6-one
(38): Yield: 1.77 g (60%) (Method b); crystals (pyridine/water) of
compound 38 do not have a well-defined m.p.; they decompose
with darkening from about 240 °C and their birefringence (polar-
ized light, crossed nicols) is lost at ca. 280 °C. IR (nujol): ν˜ ϭ 1682
(S)-7-Nitro-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a]quinoxalin-4-one
(34): Yield: 184 mg (24%) (Method a1), 1.45 g (62%) (Method b),
95 mg (8%) (Method c1), 0.63 g (53%) (Method c2); m.p. 252Ϫ254
°C (decomp., pyridine/water); a product claimed to be quinoxali-
none 34 has been described,[29] but the reported m.p. (288 °C) as
well as the spectroscopic data are completely different from those
found by us. [α]2D2 ϭ Ϫ646.8 (c ϭ 0.1, pyridine). IR (KBr): ν˜ ϭ
(CO) cmϪ1 1H NMR ([D6]DMSO): δ ϭ 10.94 (br. s, 1 H, NH),
.
7.83 (dd, J ϭ 9.2, 2.6 Hz, 1 H, 2-H), 7.66 (d, J ϭ 2.6 Hz, 1 H, 4-
H), 7.23 (m, 4 H, 8-, 9-, 10-, 11-H), 6.99 (d, J ϭ 9.2 Hz, 1 H, 1-
H), 4.95 (d, J ϭ (Ϫ)17.1 Hz, 1 H, 12-HA), 4.42 (d, J ϭ (Ϫ)17.1 Hz,
1 H, 12-HB), 4.40 (dd, J ϭ 11.6, 3.9 Hz, 1 H, 6a-H), 3.24 (dd, J ϭ
(Ϫ)16.5, 3.9 Hz, 1 H, 7-HA), 2.99 (dd, J ϭ (Ϫ)16.5, 11.6 Hz, 1 H,
7-HB) ppm. 13C NMR ([D6]DMSO): δ ϭ 165.6 (C-6), 139.9 (C-
13a), 137.9 (C-3), 132.4 (C-11a), 131.9 (C-7a), 128.8 (C-8), 126.6,
126.5, 126.3 (C-9, -10, -11), 125.8 (C-4a), 120.3 (C-2), 110.6 (C-1),
109.4 (C-4), 55.6 (C-6a), 47.9 (C-12), 31.1 (C-7) ppm. EI MS: m/z
(%) ϭ 295 (33) [Mϩ], 266 (2), 246 (3), 219 (3), 191 (2), 130 (2), 128
(2), 115 (7), 104 (100), 90 (4), 89 (3). C16H13N3O3 (295.3): calcd. C
65.08, H 4.44, N 14.23; found C 65.31, H 4.58, N 14.45.
1677 (CO) cmϪ1 1H NMR ([D6]DMSO): δ ϭ 10.71 (br. s, 1 H,
.
NH), 7.82 (dd, J ϭ 8.9, 2.6 Hz, 1 H, 8-H), 7.62 (d, J ϭ 2.6 Hz, 1
H, 6-H), 6.61 (d, J ϭ 8.9 Hz, 1 H, 9-H), 4.07 (dd, J ϭ 9.5, 6.3 Hz,
1 H, 3a-H), 3.46 (m, 2 H, 1-H), 2.22 (m, 1 H, 3-HA), 1.97 (m, 3 H,
2-H, 3-HB) ppm. 13C NMR ([D6]DMSO): δ ϭ 165.4 (C-4), 140.0
(C-9a), 136.8 (C-7), 126.5 (C-5a), 120.5 (C-8), 109.8 (C-9), 109.2
(C-6), 59.0 (C-3a), 46.5 (C-1), 27.5 (C-3), 21.7 (C-2) ppm. EI MS:
m/z (%) ϭ 233 (61) [Mϩ], 204 (31), 186 (10), 177 (100), 158 (10),
131 (31), 117 (7), 104 (7), 90 (8). C11H11N3O3 (233.2): calcd. C
56.65, H 4.75, N 18.02; found C 56.80, H 5.04, N 18.31.
7-Nitro-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a]quinoxalin-4-one (35):
Yield: 1.47 g (63%) (Method b); m.p. 256Ϫ259 °C (decomp., pyri-
dine/water). IR (KBr): ν˜ ϭ 1679 (CO) cmϪ1. Other spectroscopic
data are identical to those of S enantiomer 34. C11H11N3O3 (233.2):
calcd. C 56.65, H 4.75, N 18.02; found C 56.85, H 5.01, N 17.96.
N-Methoxyquinoxalinones 29؊31: These compounds were pre-
pared from DNP-imino acids 7, 8, and 10 following Methods a1
and a2.
1-Methoxy-4-methyl-7-nitro-3,4-dihydro-1H-quinoxalin-2-one (29):
Yield: 323 mg (45%) and 215 mg (30%) [from DNP-sarcosine (7),
Methods a1 and a2, respectively]; m.p. 169Ϫ171 °C (decomp., etha-
nol). IR (KBr): ν˜ ϭ 1703 (CO) cmϪ1. 1H NMR ([D6]DMSO): δ ϭ
7.93 (dd, J ϭ 9.0, 2.2 Hz, 1 H, 6-H), 7.74 (d, J ϭ 2.2 Hz, 1 H, 8-
H), 6.81 (d, J ϭ 9.0 Hz, 1 H, 5-H), 4.22 (s, 2 H, 3-H), 3.89 (s, 3 H,
OCH3), 2.94 (s, 3 H, 4-CH3) ppm. 13C NMR ([D6]DMSO): δ ϭ
159.1 (C-2), 141.5 (C-4a), 137.4 (C-7), 125.0 (C-8a), 121.4 (C-6),
110.2 (C-5), 106.2 (C-8), 62.5 (OCH3), 53.8 (C-3), 36.8 (4-CH3)
ppm. EI MS: m/z (%) ϭ 237 (21) [Mϩ], 206 (39), 178 (19), 160 (33),
132 (100), 120 (6), 117 (6), 104 (7), 90 (8). C10H11N3O4 (237.2):
calcd. C 50.63, H 4.67, N 17.71; found C 50.51, H 4.61, N 17.56.
3-Nitro-7,8,9,10-tetrahydro-5H,6aH-pyrido[1,2-a]quinoxalin-6-one
(36): Yield: 180 mg (26%) (Method a1), 1.61 g (65%) (Method b);
crystals (pyridine/water) of compound 36 decompose with darken-
ing from ca. 225 °C and they lose their birefringence (polarized
light, crossed nicols) at 270Ϫ280 °C, but a clear m.p. is not ob-
served. A product claimed to be quinoxalinone 36 has been de-
scribed, but the reported m.p.s (290 °C,[29] 188Ϫ190 °C[30]) as well
as the spectroscopic data[29] are completely different from those
found by us. IR (KBr): ν˜ ϭ 1676 (CO) cmϪ1 1H NMR
.
([D6]DMSO): δ ϭ 10.78 (br. s, 1 H, NH), 7.80 (dd, J ϭ 9.2, 2.7 Hz,
1 H, 2-H), 7.62 (d, J ϭ 2.7 Hz, 1 H, 4-H), 6.94 (d, J ϭ 9.2 Hz, 1
H, 1-H), 3.98 (br. d, J ϭ (Ϫ)13.0 Hz, 1 H, 10-HA), 3.91 (dd, J ϭ (S)-5-Methoxy-7-nitro-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a]quin-
11.6, 2.8 Hz, 1 H, 6a-H), 2.90 (m, J ϭ (Ϫ)13.0, 13.0, 2.4 Hz, 1 H, oxalin-4-one (30): Yield: 220 mg (25%) and 219 mg (25%) [from
2320
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 2314Ϫ2326