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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Yakovleva et al.
5ꢀAminoꢀ3ꢀdiethylaminoꢀ6ꢀ(3ꢀhydroxyꢀ3ꢀmethylbutynyl)ꢀ
in vacuo. Ketone 7 was obtained in a yield of 0.50 g (94.3%) (see
Table 1).
1,4ꢀnaphthoquinone (4b). The reaction of iodide 2 (2.20 g,
6.0 mmol) with 3ꢀmethylbutꢀ1ꢀynꢀ3ꢀol (3b) (0.90 g, 0.7 mL,
10.7 mmol) was carried out analogously to the synthesis of comꢀ
pound 4a. The reaction time was 7 min. The reaction mixture
was diluted with water and extracted with CHCl3. The chloroꢀ
form solution was filtered through an Al2O3 layer (30×50 mm).
The yield of acetylenic alcohol 4b was 1.70 g (87.0%) (see
Table 1).
B. A mixture of iodide 2 (1.10 g, 2.8 mmol) and cuprous
benzoylacetylide (0.80 g, 4.3 mmol) in DMF (30 mL) was stirred
at 140 °C under argon for 1 h, cooled, diluted with benzene
(200 mL), and repeatedly washed with water. After removal of
the solvent in vacuo, the residue was chromatographed on SiO2
(benzene and CHCl3 as the eluents). Ketone 7 was crystallized
from hexane. The yield of 0.70 g (66%).
5ꢀAminoꢀ3ꢀdiethylaminoꢀ6ꢀ(3ꢀhydroxyꢀ3ꢀphenylpropynyl)ꢀ
1,4ꢀnaphthoquinone (4c). Compound 4c was prepared analoꢀ
gously to alcohol 4b from iodide 2 (0.39 g, 1.0 mmol) and
3ꢀphenylpropꢀ1ꢀynꢀ3ꢀol (3c) (0.22 g, 0.22 mL, 1.7 mmol). The
reaction time was 20 min. The yield of compound 4c was 0.37 g
(94.9%) (see Table 1).
5ꢀAminoꢀ3ꢀdiethylaminoꢀ6ꢀ(3ꢀhydroxyꢀ4ꢀmethylpentynyl)ꢀ
1,4ꢀnaphthoquinone (4d). Compound 4d was prepared analoꢀ
gously to alcohols 4b,c from iodide 2 (0.54 g, 1.5 mmol) and
4ꢀmethylpentꢀ1ꢀynꢀ3ꢀol (3d) (0.33 g, 3.4 mmol). The condenꢀ
sation time was 10 min. The yield of alcohol 4d was 0.36 g
(79.5%) (see Table 1).
5ꢀAminoꢀ3ꢀdiethylaminoꢀ6ꢀethynylꢀ1,4ꢀnaphthoquinone (4e).
A calcined KOH powder (1.00 g, 17.8 mmol) was added with
stirring to a solution of compound 4b (2.00 g, 6.1 mmol) in
toluene (210 mL) at 70 °C. The reaction mixture was heated to
110 °C, stirred for 20 min, cooled, and filtered through a small
Al2O3 layer. The solvent was removed in vacuo. Ethynylꢀ
naphthoquinone 4e was isolated in a yield of 1.60 g (95%) (see
Table 1).
8ꢀDiethylaminoꢀ2ꢀphenylbenz[g]indoleꢀ6,9ꢀdione (5a).
A mixture of compound 4a (0.35 g, 1.0 mmol) in DMF (20 mL)
was heated in the presence of cuprous phenylacetylide (0.08 g,
0.5 mmol) and CuCl (0.05 g, 0.5 mmol) under argon at 155 °C
for 4.5 h, poured into water (400 mL), and extracted with toluꢀ
ene. The solvent was removed in vacuo. The yield of benzindoleꢀ
dione 5a was 0.29 g (82.2%) (see Table 2).
C. A mixture of benzoyl chloride (0.52 g, 0.42 mL, 4.0 mmol)
and Et3N (0.60 g, 0.84 mL, 6.0 mmol) in benzene (8 mL) was
stirred under argon (2—3 min). Then a solution of ethynylꢀ
naphthoquinone 4e (0.54 g, 2.0 mmol) in benzene (10 mL)
was added, the reaction mixture was warmed to 60 °C, and
Pd(PPh3)2Cl2 (30 mg) was added. Then the mixture was heated
to 80 °C and stirred for 5 min. Chromatography on Al2O3
(30×80 mm) in benzene afforded ketone 7 (0.30 g, 42%).
5ꢀAminoꢀ3ꢀdiethylaminoꢀ6ꢀ(4ꢀmethylꢀ3ꢀoxopentynyl)ꢀ1,4ꢀ
naphthoquinone (8). Alcohol 4d (0.80 g, 2.3 mmol) was oxidized
with the Collins reagent (7.50 g, 29.0 mmol) in CH2Cl2 (150 mL)
under the conditions of the synthesis of ketone 7. The yield of
ketone 8 was 0.60 g (78%) (see Table 1).
5ꢀAminoꢀ6ꢀbenzoylethynylꢀ3ꢀhydroxyꢀ1,4ꢀnaphthoquinone
(9). A solution of ketone 7 (0.30 g, 0.8 mmol) and HgSO4 (60 mg)
in dioxane (20 mL) acidified with 45% H2SO4 (0.3 mL) was
stirred at 85 °C for 4 h. Then the reaction mixture was cooled,
poured into water (300 mL), and extracted with CHCl3. The
organic layer was washed with water to neutral pH and dried
with MgSO4. The solvent was removed in vacuo and the residue
was triturated with hexane. Hydroxynaphthoquinone 9 was obꢀ
tained in a yield of 0.23 g (76.7%) (see Table 1).
9ꢀDiethylaminoꢀ4ꢀpiperidinoꢀ2ꢀphenylbenzo[h]quinolineꢀ
7,10ꢀdione (12a). A solution of ketone 7 (0.30 g, 0.8 mmol) in
piperidine (12 mL) was stirred at 20 °C for 45 min. After compleꢀ
tion of the reaction, the mixture was poured into water (300 mL)
and extracted with benzene 100 mL. The product was isolated
from the benzene extract with 12% HCl (2×45 mL). A hydroꢀ
chloric acid solution was gradually alkalized with a 20% aqueꢀ
ous KOH solution (260 mL) and extracted with benzene
(100 mL) as the mixture became neutral. After separation, the
aqueous alkaline layer was additionally extracted with benzene
(3×50 mL). The combined benzene extracts were washed with
water to neutral pH and dried with MgSO4. The solvent was
removed in vacuo. Compound 12a was obtained in a yield of
0.24 g (68.6%) (see Table 2).
9ꢀDiethylaminoꢀ4ꢀmorpholinoꢀ2ꢀphenylbenzo[h]quinolineꢀ
7,10ꢀdione (12b). Compound 12b was prepared analogously from
ketone 7 (0.48 g, 1.3 mmol) and morpholine (13 mL) at 20 °C
(2 h) in a yield of 0.52 g (91%) (see Table 2).
4,9ꢀBis(diethylamino)ꢀ2ꢀphenylbenzo[h]quinolineꢀ7,10ꢀdione
(12c). Compound 12c was prepared analogously from ketone 7
(0.49 g, 1.3 mmol) and Et2NH (27 mL) at 20 °C (1 h) in a yield
of 0.30 g (55.6%) (see Table 2).
9ꢀDiethylaminoꢀ2ꢀisopropylꢀ4ꢀpiperidinobenzo[h]quinolineꢀ
7,10ꢀdione (13a). Compound 13a was prepared analogously from
acetylenic ketone 8 (0.28 g, 0.8 mmol) and piperidine 18 mL at
20 °C (70 min). The yield of benzoquinolinedione 13a was 0.17 g
(51.3%) (see Table 2).
9ꢀDiethylaminoꢀ2ꢀisopropylꢀ4ꢀmorpholinobenzo[h]quinolineꢀ
7,10ꢀdione (13b). Compound 13b was prepared analogously from
ketone 8 (0.30 g, 0.9 mmol) and morpholine (9 mL) at 20 °C
8ꢀDiethylaminobenz[g]indoleꢀ6,9ꢀdione (5b). A mixture of
compound 4e (0.10 g, 0.4 mmol) and piperidine (4 mL) was
heated at 70 °C for 3.5 h. Excess piperidine was distilled off
in vacuo. The residue was dissolved in CHCl3, applied onto SiO2
(45×140 mm), and allowed to stand for 2 days. Benzindoledione
5b was washed with CHCl3 and a CHCl3—EtOH mixture. The
yield was 0.08 g (80%) (see Table 2).
8ꢀDiethylaminoꢀ2ꢀisopropenylbenz[g]indoleꢀ6,9ꢀdione (5c).
A mixture of acetylenic alcohol 4b (0.60 g, 1.8 mmol) was subꢀ
jected to cyclization in the presence of cuprous phenylacetylide
(0.15 g, 0.9 mmol) and CuCl (0.09 g, 0.9 mmol) in DMF (35 mL)
analogously to heterocyclization of compound 4a in indole 5a.
The reaction time was 5 h. Chromatography on SiO2 (toluene
and a toluene—acetone mixture as the eluents) afforded isoꢀ
propenylbenzindole 5c in a yield of 0.31 g (55.4%) (see Table 2).
5ꢀAminoꢀ6ꢀbenzoylethynylꢀ3ꢀdiethylaminoꢀ1,4ꢀnaphthoꢀ
quinone (7). A. The Collins reagent24 (1.90 g, 7.3 mmol) was
added portionwise with stirring to a cold solution of compound
4c (0.54 g, 1.4 mmol) in dry freshly distilled CH2Cl2 (75 mL) for
10 min, so that the temperature of the reaction mixture was
maintained no higher than 10 °C. The reaction mixture was
stirred at 20 °C for 1 h, diluted with CHCl3 (100 mL), and
poured into a solution of NaHCO3 (3.00 g, 35.7 mmol) in water
(70 mL). The organic layer was separated, washed with water
(3×100 mL), and dried with MgSO4. The solvent was removed