67.92; H, 3.17; N, 8.80%); IR νmax/cmϪ1: 1766, 1696, 1679, 1602,
1564, 1481, 1466, 1422, 1396, 1309, 1219, 914, 748; δH (300
MHz; 75 ЊC, DMSO-d6): 4.86 (2 H, s), 7.42 (2 H, m), 7.52 (1 H,
d, J 8.4), 7.71 (1 H, t, J and 8.4), 7.80 (1 H, d, J 7.7), 7.90 (1 H,
t, J 7.3), 8.07 (1 H, d, J 7.3); δH (500 MHz; CF3OOD): 5.44
(2 H, s), 7.64 (1 H, t, J 8), 7.73 (1 H, d, J 8), 7.82 (1 H, t, J 8),
7.94 (1 H, t, J 8), 8.11 (1 H, d, J 8), 8.16 (1 H, t, J 8), 8.44 (1 H,
d, J 8), 8.51 (1 H, d, J 8) [Coupling constants could not be
matched with higher accuracy]; δC (125 MHz; CF3OOD): 52.3
(t), 103.8 (s), 114.6 (s), 118.0 (s), 119.5 (d), 124.5 (s), 125.1 (d),
130.4 (d), 133.1 (d), 134.4 (d), 139.1 (d), 139.5 (s), 140.1 (s),
142.4 (d), 154.5 (s), 156.5 (s), 160.4 (s).
22.9 (q), 126.2 (d), 127.9 (d), 128.1 (d), 129.7 (s), 129.8 (d), 130.0
(d), 130.3 (s), 131.2 (d), 132.4 (d),133.6 (d), 141.7 (s), 142.8 (s),
167. 3 (s), 167.6 (s), 169.8 (s); δC (75 MHz; 85 ЊC, DMSO-d6):
22.7, 125.6, 127.5, 129.5, 130.4, 131.6, 132.7, 166.8, 169.2.
2,2Ј-(Trifluoroacetylimino)bis-benzoic acid (26b)
2,2Ј-Iminobis-benzoic acid (2.57 g, 10.0 mmol) was refluxed in
20 mL MeCN with 5 mL TFAA for 10 min. On cooling a crop
of 1.20 g (50%) acridone-4-carboxylic acid, mp 322 ЊC (lit.27 mp
324–325 ЊC) precipitated out of solution and was removed by
filtration. The filtrate was concentrated in vacuo and diluted
with methyl acetate, resulting in precipitation of the title com-
pound. Filtration gave 1.65 g (47%) light yellow material of 26b
which on heating (200–250 ЊC) formed acridone-4-carboxylic
acid (Found: C, 54.08; H, 2.72; N, 3.82. C16H10F3NO5 requires
C, 54.40; H, 2.85; N, 3.97%); IR νmax/cmϪ1: 3084, 3050, 2905,
2648, 2543, 1698, 1680, 1599, 1572, 1454, 1402, 1274, 1225,
1152, 757, 736; δH (300 MHz; DMSO-d6): 7.17 (1 H, dd, J 0.8
and 7.7), 7.42 (1 H, dt, J 0.8 and 7.7), 7.54–7.66 (4 H, m), 7.94
(1 H, dd, J 1.5 and 7.7), 8.12 (1 H, dd, J 1.4 and 7.7), 13.81 (2 H,
very br s); δC (75 MHz; DMSO-d6): 116.0 (s, qCF, JCF 287), 127.8
(d), 127.9 (d), 128.1 (s), 129.1 (s), 129.3 (d), 130.0 (d), 130.9 (d),
131.6 (d), 133.3 (d), 134.0 (d), 139.7 (s), 140.5 (s), 156.2 (s,
qCF, JCF 35), 166.3 (s), 166.7 (s).
7,14-Bis(trifluoroacetoxy)-6H,13H-pyrazino[1,2-a:4,5-aЈ]di-
indole-6,13-dione (21)
Compound 20 (0.63 g, 2.0 mmol) was stirred with 3.0 mL
TFAA in 15 mL MeCN at 50 ЊC for 1 h. The reaction mixture
was poured on 50 mL water, after which the product was
filtered off and washed with water. This gave 0.67 g (66%)
yellow powder, mp 385 ЊC (dec.); IR νmax/cmϪ1: 1813, 1707,
1596, 1575, 1453, 1398, 1366, 1338, 1242, 1175, 1098, 755;
When left standing in air, the compound was hydrolysed to
compound 19, and the performed elemental analysis also match
this compound (Found C, 68.10; H, 3.21; N, 8.72%). Com-
pound 21 itself proved to be very insoluble in DMSO-d6 (and
in CDCl3 and acetone-d6) and the spectra acquired at high
temperature exactly matched those of compound 19 (hydrolysis
in situ).
2-Phthalimidobenzoic acid (30)
Phthalic anhydride (16.0 g, 0.11 mol) and anthranilic acid
(13.7 g, 100 mmol) were refluxed for 3 h in 50 mL AcOH. The
hot solution was poured on 100 mL water and the solid which
formed was filtered off, washed with water and let dry. This
yielded 21.7 g (81%) white granular powder, mp 212 ЊC (lit.36
mp 217 ЊC from aq. EtOH); IR νmax/cmϪ1: 3071 (br, w), 2668
(w), 2553 (w), 1708, 1686, 1600, 1492, 1380, 1287, 1273, 1219,
1111, 1073, 892, 756, 720; δH (300 MHz; DMSO-d6): 7.55 (1 H,
dd, J 1.1 and 7.9), 7.63 (1 H, dt, J 1.1 and 7.5), 7.77 (1 H, dt,
J 1.5 and 7.5), 7.91–7.94 (2 H, m), 7.96–8.00 (2 H, m), 8.05 (1 H,
dd, J 1.5 and 7.9), 13.12 (1 H, br s); δC (75 MHz; DMSO-d6):
123.5 (d), 129.2 (d), 129.2 (s), 130.6 (d), 131.0 (d), 131.4 (s),
131.7 (s), 133.0 (d), 134.8 (d), 166.1 (s), 167.1 (s).
6a-Methyl-6,7-dioxa-12b-azabenzo[c]phenanthrene-5,8-dione
(23a)
2,2Ј-Iminobis-benzoic acid (2.57 g, 10.0 mmol) was refluxed in
25 mL Ac2O for 30 min. The crystalline material which formed
on cooling of the reaction mixture was collected and dried to
yield 2.65 g (95%) of 23a, mp 280–283 ЊC [lit.25 mp 280–287 ЊC
(dec.)]; IR νmax/cmϪ1: 1751, 1606, 1485, 1392, 1297, 1020, 962,
898, 774, 696, 523; δH (300 MHz; CDCl3): 1.94 (3 H, s), 7.16
(2 H, d, J 8.1), 7.35 (2H, dt, J 0.85 and 8.1), 7.64 (2H, dt, J 1.6
and 7.7), 8.13 (2 H, dd, J 1.6 and 7.7); δC (75 MHz; CDCl3):
26.8 (q), 110.5 (s), 117.5 (s), 121.4 (d), 125.8 (d), 131.0 (d), 135.6
(d), 142.7 (s), 159.8 (s).
Acetyl-(2-phthalimido)benzoyl anhydride (31) and 2-phthalimido-
benzoic acid anhydride (32)
6a-Trifluoromethyl-6,7-dioxa-12b-azabenzo[c]phenanthrene-
5,8-dione (23b)
Compound 30 (1.34 g, 5.00 mmol) was refluxed in 7.5 mL Ac2O
for 15 h. After cooling and evaporation in vacuo, an oil
remained. This material was extracted with 3 × 20 mL boiling
diisopropylether from which the product precipitated on co-
oling. This gave 0.58 g white needles of compound 31 (38%),
mp 135 ЊC (lit.33 mp 125 ЊC); IR νmax/cmϪ1: 1800, 1719, 1382,
1175, 1003, 716, 703; δH (300 MHz; CDCl3): 2.22 (3 H, s), 7.45
(1 H, dd, J 1.3 and 7.8), 7.58 (1 H, dt, 1.3 and 7.8), 7.77–7.83
(3 H, m), 7.93–7.98 (2 H, m), 8.14 (1 H, dd, J 1.5 and 7.8);
δC (75 MHz; CDCl3): 22.5 (q), 124.0 (d), 126.7 (s), 129.4 (d),
130.9 (d), 132.2 (s), 132.2 (d), 132.7 (s), 134.6 (d), 134.7 (d),
160.3 (s), 165.7 (s), 167.3 (s). The remaining residue was found
to be 0.81 g of compound 32 (62%). It could be triturated with
chloroform to yield a white solid, mp 295 ЊC (dec.) (lit.37 mp
287–288 ЊC); IR νmax/cmϪ1: 1791, 1717, 1383, 1208, 1016, 721,
709; δH (300 MHz, 45 ЊC, CDCl3): 7.44 (2 H, dd, J 1.0 and 7.8),
7.55 (2 H, dt, J 1.3 and 7.8), 7.70–7.78, (6 H, m), 7.87–7.96 (4 H,
m), 8.17 (2 H, dd, J 1.3 and 7.8); δC (75 MHz; 45 ЊC,CDCl3):
124.0 (d), 124.1 (d), 126.8 (s), 129.4 (d), 131.0 (d), 132.4 (d),
132.4 (s), 133.3 (s), 134.4 (d), 134.4 (d), 159.6 (s), 167.2 (s).
Compound 23b (0.70 g, 2.0 mmol) was refluxed in 5 mL Ac2O
for 5 min. On cooling crystals of the product formed and were
collected to yield 0.59 g (88%) solid material which on heating
(200–250 ЊC) formed acridone-4-carboxylic acid (Found: C,
57.79; H, 2.51; N, 4.21. C16H8F3NO4 requires C, 57.32; H, 2.41;
N, 4.18%); IR νmax/cmϪ1: 1765, 1608, 1586, 1484, 1457, 1308,
1268, 1217, 1175, 1102, 954, 772, 751; δH (300 MHz; DMSO-
d6): 7.50–7.55 (4 H, m), 7.89 (2 H, dt, J 1.2 and 7.4), 8.09 (2 H,
dd, J 1.2 and 8.1); δC (75 MHz; DMSO-d6): 103.1 (s, qCF
JCF 35), 115.0 (s), 119.5 (s, qCF, JCF 291), 121.4 (d), 126.7 (d),
130.4 (d), 137.3 (d), 139.9 (s), 156.4 (s).
,
2,2Ј-(Acetylimino)bis-benzoic acid (26a)
2,2Ј-Iminobis-benzoic acid (2.57 g, 10.0 mmol) was heated in
25 mL Ac2O for 2 min at 105 ЊC. The hot mixture was filtered
(by suction) and, on rapid cooling of the filtrate, crystals of the
product formed. This yielded 1.51 g (50%) of white solid, mp
220 ЊC (dec.) (Found: C, 64.52; H, 4.28; N, 4.72. C16H13NO5
requires C, 64.21; H, 4.38; N, 4.68%); IR νmax/cmϪ1: 3072, 3000,
2896, 2825, 1720, 1691, 1638, 1598, 1574, 1491, 1374, 1348,
1303, 1272, 1234, 1092, 770; δH (300 MHz; DMSO-d6): 1.79
(3 H, s), 7.05 (1 H, dd, J 0.8 and 8.0), 7.28 (1 H, dt, J 1.1 and
7.5), 7.43–7.62 (4 H, m), 7.79 (1 H, dd, J 1.4 and 7.7), 8.00 (1 H,
dd, J 1.1 and 7.5), 13.15 (2 H, br s); δC (75 MHz; DMSO-d6):
N-(2-Carboxybenzoyl)anthranilic acid (33)
2-Phthalimidobenzoic acid (30) (2.67 g, 10.0 mmol) was stirred
in 50 mL water with 0.40 g NaOH for 15 h. The reaction
mixture was filtered and acidified with 3 mL conc. HCl. The
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 3 9 6 – 3 4 0 3
3402