May-Jun 2001
Synthesis and Chemiluminescent Activity of 8,9-Dihydrobenzo
631
deuterium oxide exchangeable, OH), 7.23 (1H, dd, J = 8.9, J =
1
1
3
718, 1690 (CO). H-nmr (deuteriomethanol): δ 3.95, 3.98 (each
H, each s, CH x 2), 7.07 (1H, dd, J = 8.8, J = 2.4, 7-H), 7.49 (1H, d,
2
7
.4, 6'-H), 7.42 (1H, dd, J = 8.0, J = 7.4, 3'-H), 7.52 (1H, dd, J =
.4, J = 1.4, 2'- or 4'-H), 7.87 (1H, d, J = 8.9, 5'-H ), 7.99 (1H, br
3
J = 8.9, 5-H), 7.72 (1H, d, J = 8.9, 4-H), 7.76 (1H, d, J = 2.4, 9-H),
.76 (1H, d, J = 8.8, 6-H).
Anal. Calcd. for C16H13NO : C, 64.21; H, 4.38; N, 4.68.
d, J = 8.0, 2'- or 4'-H).
7
Anal. Calcd. for C H N O : C, 58.72; H, 4.00; N, 12.84.
1
6 13 3 5
5
Found: C, 58.56; H, 4.04; N, 12.53.
Dimethyl 1H-Benz[g]indole-2,3-dicarboxylates 4.
General Procedure.
Found: C, 64.59; H, 4.50; N, 4.66.
8
,9-Dihydrobenzo[g]pyridazino[4,5-b]indole-7,10(11H)-diones (5).
General Procedure.
This procedure is essentially similar to the method of Mitchell
et al. [8]. That is, solution of 3 in methanol was irradiated with a
00 watt high-pressure mercury lamp under nitrogen atmosphere.
After evaporation of the solvent the residue was directly
recrystallized or subjected to column chromatography on silica
gel for purification.
A mixture of 4 and hydrazine hydrate in ethanol (or methanol)
was refluxed for an appropriate period. After evaporation of the
solvent and excess of hydrazine hydrate, the resulting crystalline
residue was dissolved in dimethyl sulfoxide and diluted
hydrochloric acid was added to the resulting solution. Then the
precipitated crystalline solid was collected in vacuo, washed with
water and recrystallized from an appropriate solvent to afford 5.
5
Dimethyl 1H-Benz[g]indole-2,3-dicarboxylate (4a).
8
,9-Dihydrobenzo[g]pyridazino[4,5-b]indole-7,10(11H)-dione (5a).
The title compound was obtained by the method of Mitchell et
al. [8] except for the solvent. In our case methanol was
employed. Colorless needles (from benzene-n-hexane), 83%
yield, m.p. 191-191.5 °C (lit. [8] mp 191-192 °C).
A solution of 4a (1.60 g, 5.65 mmol) and hydrazine hydrate
(56.0 g, 1.12 mol) in ethanol (280 ml) was refluxed for 2.5 hours.
Recrystallization from methanol gave 5a (1.33 g, 5.30 mmol) as
white granules, 94% yield, mp >300 °C. FAB-ms m/z: 252
Dimethyl 6-Hydroxy-1H-benz[g]indole-2,3-dicarboxylate (4b).
+
-1
(
(
MH ). Ir (potassium bromide) cm : 3517, 3222, 3092, 2972
A solution of 3b (300 mg, 0.917 mmol) in methanol (600 ml)
was irradiated for 3.5 hours. Column chromatography eluting
with chloroform gave unreacted 3b (146 mg, 0.446 mmol). The
eluate using the same eluting system gave 4b (73 mg,
1
NH, broad), 1618 (CO). H-nmr (DMSO-d ): δ 7.63-7.72
6
(2H, m, J = 8, J = 1.6, 2- and 3-H), 7.75 (1H, d, J = 8.7, 5-H), 8.06
(1H, br d, J = 8, 4-H), 8.14 (1H, d, J = 8.7, 6-H), 8.80 (1H, d, J =
8, 1-H), 11.60 (2H, br s, deuterium oxide exchangeable, NH x 2),
13.45 (1H, br s, deuterium oxide exchangeable, NH).
0
.244 mmol) which was recrystallized from chloroform-n-
hexane as pale brown granules, 52% yield, mp 244-245 °C.
Anal. Calcd. for C H N O : C, 66.93; H, 3.61; N; 16.73.
Found: C, 66.84; H, 3.75; N, 16.44.
1
4 9 3 2
+
+
FAB-ms m/z: 300 (MH ), 268 (MH - 32). Ir (potassium
-
1
bromide) cm : 3430, 3320 (NH and OH), 1695, 1685 (CO).
4
7
-Hydroxy-8,9-dihydrobenzo[g]pyridazino[4,5-b]indole-
,10(11H)-dione (5b).
1
H-nmr (deuteriomethanol): δ 3.96, 3.98 (each 3H, each s,
3
CH x 2), 6.90 (1H, dd, J = 8.0, J = 1.0, 7-H), 7.39 (1H, t, J = 8.0,
8
-H), 7.86, 7.99 (each 1H, AB q, J = 9.0, 4- and 5-H), 7.94 (1H,
A solution of 4b (300 mg, 1.00 mmol) and hydrazine hydrate
dd, J = 8.0, J = 1.0, 9-H),
Anal. Calcd. for C16H13NO : C, 64.21; H, 4.38; N, 4.68.
Found: C, 64.08; H, 4.43; N, 4.59.
(24.0 g, 480 mmol) in methanol (54 ml) was refluxed for
2.5 hours. Recrystallization from ethanol gave 5b (260 mg,
0.970 mmol) as pale yellow prisms, 97% yield, mp >300 °C.
5
+
-1
FAB-ms m/z: 268 (MH ). Ir (potassium bromide) cm : 3210,
Dimethyl 7-Hydroxy-1H-benz[g]indole-2,3-dicarboxylate (4c).
3
055 (NH and OH, broad), 1655 (CO, broad). 1H-nmr
A solution of 3c (100 mg, 0.306 mmol) in methanol (500 ml)
was irradiated for 10 minutes. Column chromatography eluting
with chloroform-ethyl acetate (17:3, v/v) gave 4c (52.3 mg,
(DMSO-d ): δ 6.99 (1H, d, J = 8.0, 3-H), 7.44 (1H, t, J = 8.0,
6
2-H), 7.99, 8.05 (each 1H, AB q, J = 8.0, 5- and 6-H), 8.22
(1H, d, J = 8.0, 1-H), 10.23 (1H, br s, deuterium oxide exchange-
able, OH), 11.55 (2H, br s, deuterium oxide exchangeable, NH
x 2), 13.27 (1H, br s, deuterium oxide exchangeable, NH).
Anal. Calcd. for C H N O : C, 62.92; H, 3.39; N; 15.72.
0
.175 mmol) which was recrystallized from ethyl acetate-n-
hexane as pale yellow granules, 57% yield, mp 246-247 °C.
+
+
FAB-ms m/z: 300 (MH ), 268 (MH - 32). Ir (potassium
1
4 9 3 3
-
1
bromide) cm : 3395, 3325 (NH and OH), 1702, 1680 (CO).
H-nmr (deuteriomethanol): δ 3.96, 3.97 (each 3H, each s,
CH x 2), 7.14 (1H, dd, J = 8.8, J = 2.4, 8-H), 7.21 (1H, d, J = 2.4,
Found: C, 63.06; H, 3.58; N, 15.63.
1
3
7
-Hydroxy-8,9-dihydrobenzo[g]pyridazino[4,5-b]indole-
,10(11H)-dione (5c).
3
6
(
-H), 7.42 (1H, d, J = 9.0, 5-H), 7.83 (1H, d, J = 9.0, 4-H), 8.34
1H, d, J = 8.8, 9-H).
Anal. Calcd. for C16H13NO : C, 64.21; H, 4.38; N, 4.68.
A solution of 4c (1.25 g, 4.18 mmol) and hydrazine hydrate
(33.0 g, 660 mmol) in ethanol (22 ml) was refluxed for 5 hours.
5
Found: C, 64.06; H, 4.51; N, 4.41.
Recrystallization from ethanol-n-hexane gave 5c (1.03 g,
3
.86 mmol) as white granules, 92% yield, mp >300 °C. FAB-ms
Dimethyl 8-Hydroxy-1H-benz[g]indole-2,3-dicarboxylate (4d).
+
-1
m/z: 268 (MH ). Ir (potassium bromide) cm : 3200, 3060 (NH
and OH, broad), 1635 (CO). H-nmr (DMSO-d ) δ: 7.16 (1H, dd,
J = 9, J = 2, 2-H), 7.28 (1H, d, J = 2, 4-H), 7.51 (1H, d, J = 9,
5-H), 8.02 (1H, d, J = 9, 6-H), 8.62 (1H, d, J = 9, 1-H), 9.84 (1H,
br s, deuterium oxide exchangeable, OH), 11.51 (2H, br s,
deuterium oxide exchangeable, NH x 2), 13.24 (1H, br s,
deuterium oxide exchangeable, NH).
1
A solution of 3d (300 mg, 0.917 mmol) in methanol (500 ml) was
irradiated for 45 minutes. Column chromatography eluting with
chloroform-ethyl acetate (17:3, v/v) gave 4d (142 mg, 0.475 mmol)
which was recrystallized from chloroform-n-hexane as pale yellow
6
+
granules, 52% yield, mp 247-248 °C. FAB-ms m/z: 300 (MH ), 268
+
-1
(
MH - 32). Ir (potassium bromide) cm : 3445, 3280 (NH and OH),