Annelation of drotaverine by pꢀquinones
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 3, March, 2005
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Table 2. 1H NMR spectra of compounds 5, 11a—h, and 12
Comꢀ
pound
CDCl3, δ (J/Hz)
5
1.18 (t, 3 Н, Me, J = 7.0); 1.30—1.50 (m, 9 H, 3 Me); 3.15 (t, 2 H, С(12)Н2, J = 6.5); 3.62 (q, 2 H, СН2,
J = 7.0); 4.00—4.20 (m, 6 H, 3 СН2); 4.82 (t, 2 H, С(13)H2, J = 6.5); 5.05 (s, 1 Н, ОН); 6.76 (s, 1 H, С(11)Н);
6.86 (s, 1 H, С(2´)Н); 6.93 (s, 1 H, С(6)Н); 6.95—7.05 (m, 3 H, СНarom); 7.40—7.60 (m, 2 H, С(2)Н+С(3)Н);
8.25—8.45 (m, 2 H, С(1)Н+С(4)Н)
11а
11b
11c
11d
11e
11f
11g
11h
12
1.20 (t, 3 H, Me, J = 7.0); 1.35—1.55 (m, 9 H, 3 Me); 3.14 (t, 2 H, С(12)Н2, J = 6.5); 3.63 (q, 2 H, СН2,
J = 7.0); 3.93 (s, 3 H, ОMe); 4.00—4.25 (m, 6 H, 3 СН2); 4.81 (t, 2 H, С(13)H2, J = 6.5); 6.76 (s, 1 H, С(11)Н);
6.86 (s, 1 H, С(2´)Н); 6.90 (s, 1 H, С(6)Н); 6.95—7.05 (m, 2 H, СНarom); 7.07 (s, 1 H, С(8)Н); 7.35—7.60
(m, 2 H, С(2)Н+С(3)Н); 8.36 (m, 2 H, С(1)Н+С(4)Н)
1.19 (t, 3 H, Me, J = 7.0); 1.35—1.55 (m, 9 H, 3 Me); 3.14 (t, 2 H, С(12)Н2, J = 6.5); 3.62 (q, 2 H, СН2,
J = 7.0); 4.00—4.20 (m, 8 H, 4 СН2); 4.81 (t, 2 H, С(13)H2, J = 6.5); 6.75 (s, 1 H, С(11)Н); 6.85 (s, 1 H,
С(2´)Н); 6.90 (s, 1 H, С(6)Н); 6.95—7.04 (m, 2 H, СНarom); 7.05 (s, 1 H, С(8)Н); 7.35—7.60 (m, 2 H,
С(2)Н+С(3)Н); 8.30—8.50 (m, 2 H, С(1)Н+С(4)Н)
1.09 (t, 3 H, Me, J = 7.4); 1.19 (t, 3 H, Me, J = 7.0); 1.35—1.55 (m, 9 H, 3 Me); 1.91 (m, 2 H, СН2); 3.14
(unres. t, С(12)Н2); 3.63 (q, 2 H, СН2, J = 7.0); 3.90—4.30 (m, 8 H, 4 СН2); 4.81 (t, 2 H, С(13)H2, J = 6.5);
6.75 (s, 1 H, С(11)Н); 6.86 (s, 1 H, С(2´)Н); 6.89 (s, 1 H, С(6)Н); 6.95—7.05 (m, 2 H, СНarom); 7.06 (s, 1 H,
С(8)Н); 7.35—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.30—8.50 (m, 2 H, С(1)Н+С(4)Н)
1.20 (t, 3 H, Me, J = 7.0); 1.38 (d, 6 H, 2 Me, J = 6.0); 1.40—1.60 (m, 9 H, 3 Me); 3.14 (t, 2 H, С(12)H2,
J = 6.5); 3.63 (q, 2 H, СН2, J = 7.0); 4.00—4.25 (m, 6 H, 3 СН2); 4.60 (quint, 1 H, СН, J = 6.0); 4.81
(t, 2 H, С(13)Н2, J = 6.5); 6.75 (s, 1 H, С(11)Н); 6.86 (s, 1 H, С(2´)Н); 6.97 (s, 1 H, С(6)Н); 7.06 (s, 1 H,
С(8)Н); 7.35—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.37 (m, 2 H, С(1)Н+С(4)Н)
0.98 (t, 3 H, Me, J = 7.4); 1.20 (t, 3 H, Me, J = 7.0); 1.30—1.70 (m, 11 H, СН2+3 Me); 1.87 (m, 2 H, СН2);
3.14 (unres. t, С(12)Н2); 3.63 (q, 2 H, СН2, J = 7.0); 4.00—4.25 (m, 8 H, 4 СН2); 4.81 (t, 2 H, С(13)H2,
J = 6.5); 6.75 (s, 1 H, С(11)Н); 6.86 (s, 1 H, С(2´)Н); 6.89 (s, 1 H, С(6)Н); 6.95—7.05 (m, 2 H, СНarom);
7.06 (s, 1 H, С(8)Н); 7.35—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.30—8.50 (m, 2 H, С(1)Н+С(4)Н)
1.09 (br.d, 6 H, 2 Me); 1.20 (t, 3 H, Me, J = 7.0); 1.30—1.60 (m, 9 H, 3 Me); 2.21 (m, 1 H, СН), 3.14
(unres. t, 2 H, С(12)Н2); 3.63 (q, 2 H, СН2, J = 7.0); 3.81 (d, 2 H, СН2, J = 6.3); 4.00—4.20 (m, 6 H, 3 СН2);
4.81 (t, 2 H, С(13)H, J = 6.5); 6.75 (s, 1 H, С(11)Н); 6.86 (s, 1 H, С(2´)Н); 6.87 (s, 1 H, С(6)Н); 6.95—7.05
(m, 2 H, СНarom); 7.06 (s, 1 H, С(8)Н); 7.35—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.30—8.50 (m, 2 H, С(1)Н+С(4)Н)
1.20 (t, 3 H, Me, J = 7.0); 1.30—1.60 (m, 9 H, 3 Me); 2.46 (t, 1 H, ≡СН, J = 2.35); 3.14 (t, 2 H, С(12)Н2,
J = 6.5); 3.63 (q, 2 H, СН2, J = 7.0); 4.00—4.20 (m, 6 H, 3 СН2); 4.80 (m, 4 H, С(13)Н2+СН2С≡); 6.76
(s, 1 H, С(11)Н); 6.87 (s, 1 H, С(2´)Н); 6.99 (s, 1 H, С(6)Н); 7.00—7.10 (m, 2 H, СНarom); 7.05 (s, 1 H,
С(8)Н); 7.40—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.38 (m, 2 H, С(1)Н+С(4)Н)
1.19 (t, 3 H, Me, J = 7.0); 1.30—1.60 (m, 9 H, 3 Me); 2.42 (s, 3 H, COCH3); 3.14 (t, 2 H, С(12)Н2, J = 6.5);
3.63 (q, 2 H, СН2, J = 7.0); 3.90—4.30 (m, 6 H, 3 СН2); 4.84 (t, 2 H, С(13)Н2, J = 6.5); 6.76 (s, 1 H, С(11)Н);
6.88 (s, 1 H, С(2´)Н); 6.90—7.10 (m, 3 H, СНarom); 7.32 (s, 1 H, С(6)Н); 7.40—7.60 (m, 2 H, С(2)Н+С(3)Н);
7.89 (d, 1 H, С(1)Н, J = 8.5); 8.43 (d, 1 H, С(4)Н, J = 8.5)
1.15 (t, 3 H, Me, J = 7.0); 1.30—1.60 (m, 9 H, 3 Me); 1.87 (m, 2 H, СН2); 2.40 (unres. t, 4 H, (СН2)2N);
3.10 (t, 2 H, С(12)H2, J = 6.5); 3.56 (m, 4 H, 2 СН2); 3.68 (unres. t, 4 H, (СН2)2О); 3.90—4.30 (m, 6 H,
3 СН2); 4.83 (m, 2 H, СН2); 6.58 (s, 1 H, С(11)Н); 6.72 (s, 1 H, С(2´)Н); 6.90—7.10 (m, 3 H, СНarom);
7.30—7.60 (m, 2 H, С(2)Н+С(3)Н); 8.35 (m, 2 H, С(1)Н+С(4)Н); 11.80 (s, 1 H, ОН)
melting at 175—180 °C. IR, ν/cm–1: 3390 br (OH), 1615, 1600,
1575, 1548 (arom.). Found (%): C, 73.51; H, 6.39; N, 3.11.
C30H33NO5. Calculated (%): C, 73.90; H, 6.82; N, 2.87.
(68%); m.p. 130—135 °C (from CH3CN), solidification, reꢀ
peated melting at 190 °C. IR, ν/cm–1: 3465 (OH), 1620, 1600,
1580, 1540 (arom.). Found (%): C, 75.60; H, 6.52; N, 3.00.
C34H35NO5. Calculated (%): C, 75.95; H, 6.56; N, 2.61.
7ꢀ(3´,4´ꢀDiethoxyphenyl)ꢀ9,10ꢀdiethoxyꢀ5ꢀhydroxyꢀ
7a,12,13,14ꢀtetrahydrobenz[g]indolo[2,1ꢀa]isoquinoline (5).
Drotaverine (16.0 g, 0.04 mol) and pꢀnaphthoquinone (7.0 g,
0.044 mol) were ground in a mortar and fused in a 250ꢀmL
conical flask on a boiling water bath. After completion of the
exothermic reaction, during which the temperature raised to
145—150 °C, the mixture was slightly cooled, MeOH (150 mL)
was added, and the mixture was refluxed with grinding using a
glass rod until the reaction product turned into a powdered
precipitate. Then the mixture was cooled with cold water and
the precipitate was filtered off and dried. The yield was 14.5 g
5ꢀ(3,4ꢀDiethoxyphenyl)ꢀ7,8ꢀdiethoxyꢀ3ꢀmethoxyꢀ
5a,10,11,12ꢀtetrahydroindolo[2,1ꢀa]isoquinoline (10a). Sodium
hydroxide (0.24 g, 0.006 mol) was ground in a 25ꢀmL coniꢀ
cal flask under DMSO (5 mL). Then compound 4 (1.46 g,
0.003 mol) was added, the mixture was stirred with a glass rod
for 10 min, and CH3I (0.4 mL, 100% excess) was added. After
12 h, CH3OH (10 mL) was added and the mixture was cooled
with ice. The precipitate that formed was filtered off and recrysꢀ
tallized from PriOH (50 mL). The colorless compound, m.p.
145 °C. The yield was 1.05 g (70%). Found (%): C, 74.47;