Nov-Dec 2007
Studies on Synthesis of the Azocino[4,3-b]indole Framework and Related Compounds
1321
(m, 2H), 3.22-3.65 8m, 13H), 4.40 (t, 1H, J=5.3 Hz), 5.78 (s,
1H), 7.27-7.30 (m, 2H), 7.39-7.41 (m, 1H), 8.19-8.21 (m, 1H),
9.10 (s, 1H). Anal. Calcd for C20H24N2O3S2: C 59.37; H 5.97; N
6.92. Found: C 59.39; H 6.00; N 6.93.
ether to give 2.6 g, 86% of 15, mp 185 °C; ir (potassium bromide):
ꢀ 3450, 1718, 1626, 1496, 748 cm-1; 1H nmr (deuterio-
dimethylsulfoxide): ꢁ 2.33-2.39 (q, 1H), 2.58-2.64 (q, 1H), 2.86
(d, 1H, J=15.49 Hz), 2.95-3.11 (m, 2H), 3.34 (s, 3H), 3.54-3.60
(m, 1H), 3.68-3.80 (m, 3H), 5.90 (dd, 2H, J=10.22 and 22.37
Hz), 7.25-7.36 (m, 2H), 7.66 (d, 1H, J=8.22 Hz), 8.09 (d, 1H,
J=7.81 Hz), 12.44 (bs, 1H); 13C nmr (deuteriodimethyl-
sulfoxide): ꢁ 36.57, 41.86, 42.05, 42.78, 48.14, 56.07, 60.21,
67.63, 75.04, 112.44, 114.22, 121.36, 123.49, 123.62, 124.86,
138.46, 147.69, 173.55, 191.97. Anal. Calcd for C18H19NO4S2: C
57.27; H 5.07; N 3.71. Found: C 57.29; H 5.04; N 3.72.
N-(2-Methoxyethyl)-6-(1,2-dithiolane-2-yl)-1,2,3,4,5,6-hexa-
hydro-1,5-methanoazocino[4,3-b]indole-3-one (12). Compound
12 was prepared according to the general procedure from 8 (5.0 g,
12.81 mmoles) and (5.0 g, 132 mmoles) sodium borohydride. The
residue was crystallized from ethyl acetate to give 4.3 g, 89% of
12, mp 244 °C; ir (potassium bromide): ꢀ 3269, 2936, 1616, 1452,
1
752 cm-1; H nmr (deuteriodimethylsulfoxide): ꢁ 2.33-2.36 (m,
1H), 2.44-2.61 (m, 3H), 2.79-2.85 (m, 2H), 3.13-3.20 (m, 1H), 3.26
(s, 3H), 3.48-3.63 (m, 4H), 3.73-3.79 (m,1H), 3.95-4.06 (m, 1H),
4.79 (t, 1H), 7.00-7.13 (m, 1H), 7.34 (d, 1H, J=8.06 Hz), 7.57 (d,
1H, J=7.84), 11.22 (s, 1H); 13C nmr (deuteriodimethylsulfoxide): ꢁ
31.14, 32.75, 36.60, 41.60, 43.04, 45.88, 48.22, 58.69, 70.02,
70.39, 112.14, 113.57, 119.11, 119.81, 122.59, 125.13, 134.48,
137.01, 168.87; ms: m/z 374 (77) [M]+, 316 (88), 240 (60), 212
(100), 180 (58), 167 (58). Anal. Calcd for C19H22N2O2S2: C 60.93;
H 5.92; N 7.47. Found: C 60.91; H 5.93; N 7.46.
N-(2-Methoxyethyl){9-methoxymethylene-2,3,4-tetrahydro-
spiro[1H-carbazole-1,2'[1,3]dithiolane-4-one]-2-yl}-2-acetamide
(16). Compound 16 was obtained according to the preparation of
5 from 15 (3.0 g, 7.94 mmoles) and methoxyethylamine (2.0 g,
26.6 mmoles). The residue was crystallized from diethyl ether to
give 3.1 g, 89% of 16, mp 119 °C; ir (potassium bromide): ꢀ
3286, 1680, 1638, 1552, 748 cm-1; 1H nmr (deuteriochloroform):
ꢁ 2.27-2.33 (q, 1H), 2.65-2.71 (q, 1H), 3.05-3.20 (m, 1H), 3.24-
3.29 (m, 2H), 3.37, (s, 3H), 3.41 (s, 3H), 3.44-3.49 (m, 4H),
3.56-3.69 (m, 4H), 5.87 (d,1H, J=10.20 Hz), 6.00 (d, 1H,
J=10.20 Hz), 7.29-7.38 (m, 2H), 7.56-7.58 (q, 1H), 8.30-8.33 (q,
1H). Anal. Calcd for C21H26N2O4S2: C 58.03; H 6.03; N 6.44.
Found: C 58.04; H 6.07; N 6.41.
N-(2-Benzyloxyethyl)-7-methyl-6-(1,2-dithiolane-2-yl)-1,2,
3,4,5,6-hexahydro-1,5-methanoazocino[4,3-b]indole-3-one
(13). Compound 9 (1.0, g, 2.2 mmoles) and (0.5 g,10.4 mmoles,
50% suspension in paraffin oil) of sodium hydride and 2 mL
iodomethane in 20 mL benzene were refluxed for 6 h. After
cooling the mixture, 2 mL methanol, and then 20 mL water were
added. The organic layer was separated and evaporated. The
residue was purified by using column chromatography and
crystallized from n-hexane to give 0.85 g, 80% of 13, mp 146
N-(2-Methoxyethyl)-6-(1,2-dithiolane-2-yl)-7-methoxymeth-
ylene-1,2,3,4,5,6-hexahydro-1,5-methano-2-azocino[4,3-b]-
indole-3-one (17). Compound 17 was obtained according to the
preparation of 9 from 16 (3.0 g, 6.9 mmoles) and (3.0 g, 79.3
mmoles) sodium borohydride. Subsequent purification by silica
gel chromatography using chloroform-acetone (4:1) yielded 2.2 g,
76% of 17, mp 139 °C (from diethyl ether); ir (potassium
1
°C; ir (potassium bromide): ꢀ 2953, 1628, 1464, 742 cm-1; H
nmr (deuteriochloroform): ꢁ 1.38 (d, 3H), 2.26-2.31 (m, 2H),
2.48 (d, 1H, J=12.90 Hz), 2.75-2.80 (m, 1H), 3.17-3.23 (m, 1H),
3.29-3.36 (m, 1H), 3.39-3.46 (m 1H), 3.48-3.52 (m, 2H), 3.61-
3.72 (m, 2H), 3.90 (s, 3H), 4.11-4.16 (m, 1H), 4.51 (t, 2H, J=
12.68 Hz), 4.85 (s, 1H), 7.03 (t, 1H, J=7.37 Hz), 7.13-7.31 (m,
7H), 7.56 (d, 1H, J=7.87 Hz). Anal. Calcd for C26H32N2O2S2: C
67.74; H 6.31; N 5.85. Found: C 67.75; H 6.28; N 5.83.
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bromide): ꢀ 2939, 1638, 1465, 1112, 757 cm-1; H nmr (deuterio-
chloroform): ꢁ 2.35-2.40 (m, 1H), 2.65-2.76 (m, 2H), 2.87-2.92
(m, 1H), 3.07 (d, 1H, J=19.34 Hz), 3.36.3.39 (m, 2H), 3.42 (s,
3H), 3.44 (s, 3H), 3.46-3.66 (m, 5H), 4.21-4.26 (m, 1H), 4.89 (t,
1H, J=2.33 Hz), 5.70 (d, 1H, J=10.20 Hz), 5.94 (d, 1H, J=10.20
Hz), 7.16-7.38 (m, 2H), 7.54 (d, 1H, J=8.30 Hz), 7.65 (d, 1H,
J=7.87 Hz); 13C nmr (deuteriochloroform): ꢁ 31.99, 36.29,
39.65, 41.19, 44.45, 46.74, 49.34 55.78, 59.07, 70.51, 71.67,
75.27, 111.29, 116.90, 118.84, 120.90, 123.61, 125.11, 130.52,
138.53, 169.48. Anal. Calcd for C21H26N2O3S2: C 60.25; H 6.26;
N 6.69. Found: C 66.26; H 6.24; N 6.71.
N-(2-Methoxyethyl)-4-ethyl-6-(1,2-dithiolane-2-yl)-7-meth-
oxymethylene-1,2,3,4,5,6-hexahydro-1,5-methanoazocino-
[4,3-b]indole-3-one (18). Amide 17 (1.0 g, 2.4 mmol) was
dissolved in tetrahydrofuran. To this solution (0.2 g, 4.2
mmoles, 50% suspension in paraffin oil) sodium hydride, 2 mL
iodoethane were added and refluxed for 16 h. The mixture was
poured into 30 mL 10% sodium hydroxide solution, extracted
with ethyl acetate. The organic layer was dried over anhydrous
magnesium sulfate and the solvent was evaporated. The residue
was purified by silica gel chromatography using chloroform-
acetone (4:1) and crystallized from diethyl ether-n-hexane (0.98
g, 92%), mp 136 ºC; ir (potassium bromide): ꢀ 2929, 1633, 1459
759 cm-1; 1H nmr (deuteriochloroform): ꢁ 1.05 (t, 3H, J=7.4 Hz),
1.85-1.95 (m, 1H), 2.10-2.18 (m, 1H), 2.31-2.36 (m, 1H), 2.49
(d, 1H, J=0.93 Hz), 2.63 (d, 1H, J=13.17 Hz), 2.89-2.91 (m,
1H), 3.32-3.39 (m, 2H), 3.41 (s, 3H), 3.43 (s, 3H), 3.53-3.68 (m,
5H), 4.22-4.27 (m, 1H), 4.86 (t, 1H, J=2.43 Hz), 5.70 (d, 1H,
J=10.25 Hz), 5.96 (d, 1H, J=10.24 Hz), 7.15-7.29 (m, 2H), 7.53
(d, 1H, J=8.26 Hz), 7.65 (d, 1H, J=7.86 Hz); 13C nmr
(deuteriochloroform): ꢁ 10.67, 28.10, 31.26, 39.77, 41.02, 45.89,
Ethyl{9-methoxymethylene-2,3,4-tetrahydrospiro[1H-car-
bazole-1,2'[1,3]dithiolane-4-one]-2-yl}-2-acetate (14). A
mixture of (10.0 g, 27.6 mmoles) of 4-oxo-ester 3, (0.5 g, 1.47
mmoles) tetrabutylammonium hydrogen sulfate and 30 mL 25%
sodium hydroxide in 150 mL dichloromethane was cooled in ice
bath. 8 mL methoxymethylbromide was added dropwise and
stirred for 2 h. Later on, phases were separated by adding 50 mL
water. Organic layer was dried over with anhydrous magnesium
sulfate, and evaporated. The residue was crystallized from
diethyl ether to give 104 g, 92% of 14, mp 108 °C; ir (potassium
1
bromide): ꢀ 2971, 1715, 1621, 1495, 1418, 742 cm-1; H nmr
(deuteriochloroform): ꢁ 1.28 (t, 3H, J= 7.14 Hz), 2.50-2.57 (q,
1H), 2.71-2.77 (q, 1H), 3.10-3.26 (m, 3H), 3.40 (s, 3H), 3.57-
3.71 (m, 4H), 4.14-4.20 (q, 2H), 5.88 (d, 1H, J=10.34 Hz), 6.00
(d, 1H, J=10.34 Hz), 7.29-7.37 (m, 2H), 7.56-7.58 (q, 1H), 8.31-
8.33 (q, 1H). Anal. Calcd for C20H23NO4S2: C 59.23; H 5.71; N
3.45. Found: C 59.23; H 5.73; N 3.46.
{9-Methoxymethylene-2,3,4-tetrahydrospiro[1H-carba-
zole-1,2'[1,3]dithiolane-4-one]-2-yl}-2-acetic acid (15).
Ketoester 14 (3.0 g, 7.4 mmoles) was dissolved in 15 mL tetra-
hydrofuran and 30 mL 20% potassium hydroxide (methanol-water
1:1) was added and stirred for 4 h at room temperature. This
solution was poured into 50 mL cold solution of 10% of
hydrochloric acid and extracted with ethyl acetate. The organic
layer was evaporated and the residue was crystallized from diethyl