4
32
H. Brunner et al.
PAPER
1
H NMR (CDCl , 400 MHz): d = 7.27 (ddd, 1 H, J = 7.6, J5,6
=
evaporated. To remove the excess of Ph P the residue was washed
with petroleum ether until TLC analysis did not show any residual
3
5,4
3
4
(
7
.8, J5,3 = 1.0 Hz, py-H5), 7.33 (ddd, 1 H, J = 8.4, 6.9, 1.3 Hz), 7.38
ddd, 1 H, J = 8.4, 7.0, 1.2 Hz), 7.49 (ddd, 1 H, J = 8.2, 6.9, 1.2 Hz),
.53 (dd, 1 H, J = 8.5, 0.8 Hz), 7.60Ð7.70 (m, 4 H), 7.74 (ddd, 1 H,
J4,5 ≈ J4,3 = 7.6, J4,6 = 1.8 Hz, py-H4), 7.96 (d, 1 H, J = 8.2 Hz), 8.01
Ph P. The nearly colourless product was recrystallized from ace-
3
tone/petroleum ether at Ð25¡C; yield: 2.74 g (67%); mp 219¡C.
IR (KBr): n = 2980, 2960, 2890, 2850 (CÐH aliph), 1625 (C=N),
(
(
=
dd, 1 H, J = 6.4, 2.7 Hz), 8.05 (d, 1 H, J = 8.3 Hz, isoquin-H5), 8.53
ddd, 1 H, J3,4 = 8.0, J3,5 ≈ J3,6 = 1.0 Hz, py-H3), 8.74 (ddd, 1 H, J6,5
4.8, J6,4 = 1.8, J6,3 = 1.0 Hz, py-H6), 8.90 (d, 1 H, J45 = 0.7 Hz,
Ð1
1
575s cm (C=C).
1
H NMR (CDCl , 250 MHz): d = 4.30 (s, 6 H, OCH ), 7.51 (ddd, 2
3
3
H, J = 8.2, 7.0, 1.2 Hz), 7.65 (ddd, 2 H, J = 8.2, 7.0, 1.3 Hz), 7.87
isoquin-H4).
(d, 2 H, J = 8.2 Hz), 8.25 (d, 2 H, J = 8.2 Hz), 8.42 (s, 2 H, H-4,4').
13
C NMR (CDCl , 100 MHz): d = 117.2, 121.7, 123.3, 125.2, 125.9,
3
13
C NMR (CDCl , 63 MHz): d = 53.6 (OCH ), 111.7, 119.9 (quart
1
1
26.2, 126.2, 127.4, 127.7, 127.8, 128.1, 128.2, 128.3 (quart C),
28.8, 130.3, 132.4 (quart C), 133.7 (quart C), 136.9, 137.2 (quart
3
3
C), 124.2, 126.5, 127.2, 130.4, 138.9 (quart C), 147.2 (quart C),
60.3 (quart C).
1
C), 137.3 (quart C), 149.0 (quart C), 149.2 (quart C), 156.6 (quart
C), 159.9.
MS (EI, 70 eV): m/z (%) = 316 (100, M+).
+
+
MS (EI, 70 eV): m/z (%) = 332 (77, M ), 331 (100, [MÐH] ).
Anal. calcd for C H N O (316.4): C 75.93, H 5.10, N 8.86; found:
20
16
2
2
C 75.83, H 5.25, N 8.68.
Anal. calcd for C H N (332.4): C 86.72, H 4.85, N 8.43; found:
2
4
16
2
C 86.55, H 4.81, N 8.37.
1
,1'-Dichloro-3,3'-biisoquinoline (10)
rac-1-(2-Methyl-1-naphthyl)-3-(2-pyridyl)isoquinoline (6)
The synthesis was carried out analogous to the preparation of 5, us-
ing 4 (3.88 g, 16.1 mmol), (Ph P) Pd (550 mg, 0.48 mmol), ethylene
Under exclusion of moisture the compound 9 (300 mg, 0.95 mmol)
was suspended in POCl and the mixture was refluxed for 36 h. The
3
3
4
hot solution was poured onto ice and the mixture was brought to a
pH of 10 with solid NaOH, causing precipitation. The precipitate
glycol dimethyl ether (40 mL), 2 (3.00 g, 16.1 mmol) and a 2 M
Na CO solution (16.1 mL, 32.2 mmol); yield: 3.97 g (71%); mp
was filtered, washed with H O and dried in vacuo over solid KOH.
2
3
2
1
58¡C.
Recrystallization from CHCl resulted in a colourless powder;
3
yield: 280 mg (91%); mp >250¡C.
IR (KBr): n = 3050, 3010 (CÐH arom), 2950, 2910 (CÐH aliph),
Ð1
1
620 (C=N), 1580, 1565 (C=C) cm .
IR (KBr): n = 3050 (CÐH arom), 1625 (C=N), 1575, 1565 (C=C).
MS (EI, 70 eV): m/z (%) = 324 (100, M ) rel. to 79Br.
Anal. calcd for C H Cl N (325.2): C 66.48, H 3.10, N 8.61;
1
+
H NMR (CDCl , 400 MHz): d = 2.16 (s, 3 H, CH ), 7.11 (d, 1 H,
3
3
J = 8.5 Hz), 7.22Ð7.26 (m, 1 H), 7.29 (ddd, 1 H, J= 7.5, 4.8, 1.2 Hz),
18
10
2
2
7.37Ð7.43 (m, 3 H), 7.52 (d, 1 H, J = 8.4 Hz), 7.66Ð7.70 (m, 1 H),
7.75 (ddd, 1 H, J ≈ J' = 7.7, J = 1.8 Hz), 7.91 (d, 1 H, J = 8.2 Hz),
7.94 (d, 1 H, J = 8.5 Hz), 8.07 (d, 1 H, J = 8.3 Hz, isoquin-H5), 8.50
found: C 66.64, H 3.22, N 8.37.
1
,1'-Bis(2-methoxy-1-naphthyl)-3,3'-biisoquinoline (11)
The synthesis of 11 was carried out analogous to the preparation of
, starting from 10 (150 mg, 0.46 mmol), (Ph P) Pd (32 mg,
(ddd, 1 H, J = 8.0, J≈ J3,6 = 1.0 Hz, py-H3), 8.75 (ddd, 1 H, J = 4.8,
1
.8, J6,3 = 1.0 Hz, py-H6), 8.89 (s, 1 H, isoquin-H4).
5
3
4
1
3
C NMR (CDCl , 100 MHz): d = 20.2 (CH ), 117.1, 121.9, 123.2,
3
3
0.028 mmol), ethylene glycol dimethyl ether (8 mL), boronic acid 3
186 mg, 0.92 mmol) and a 2 M Na CO solution (1 mL, 2 mmol).
1
25.0, 125.9, 126.2, 127.2, 127.7, 127.9, 128.2, 128.4, 128.5 (quart
(
2
3
C), 128.8, 130.4, 132.1 (quart C), 133.0 (quart C), 134.4 (quart C),
Reaction time was 36 h; yield: 136 mg (52%); mp > 250¡C. Spec-
troscopic data given in ref. 5 have been confirmed.
1
1
35.2 (quart C), 136.9, 137.2 (quart C), 149.2, 149.6 (quart C),
56.8 (quart C), 160.0 (quart C).
+
+
MS (EI, 70 eV): m/z (%) = 568 (49, M ), 553 (100, [MÐCH ] ).
3
+
+
MS (EI, 70 eV): m/z (%) = 346 (67, M ), 345 (100, [MÐH] ).
Anal. calcd for C H N O (568.7): C 84.48, H 4.96, N 4.93; found:
40
28
2
2
Anal. calcd for C H N (346.4): C 86.68, H 5.24, N 8.09; found:
2
5
18
2
C 84.77, H 5.12, N 4.99.
C 86.79, H 5.22, N 8.01.
1
-Bromo-2,3-dimethoxynaphthalene (19)
rac-1-(2-Methoxy-1-naphthyl)-3-(2-pyridyl)isoquinoline (7)
The synthesis was carried out analogously to the synthesis of 5,
starting from 4 (5.36 g, 22.3 mmol), (Ph P) Pd (825 mg,
To a stirred solution of 18 (5.00 g, 26.6 mmol) in CH Cl (50 mL),
protected from light and cooled to 0¡C, was added slowly a solution
of Br (4.25 g, 26.6 mmol) in CH Cl (30 mL) and the stirring was
continued for 30 min. The dark brown reaction mixture was allowed
to warm to r.t. and washed with satd NaHCO solution (3 × 20 mL)
and H O (3 × 20 mL). The organic phase was dried (Na SO ). After
the solvent was removed, the residue was dissolved in toluene and
filtered through silica gel. The solvent was evaporated and the resi-
2
2
3
4
2
2
2
0
.71 mmol), ethylene glycol dimethyl ether (60 mL), 3 (4.50 g,
2
2.3 mmol) and a 2 M Na CO solution (22.3 mL, 44.6 mmol);
2
3
3
yield: 5.71 g (15.8 mmol, 71%); mp 156¡C. Spectroscopic data giv-
en in ref. 5 have been confirmed.
MS (EI, 70 eV): m/z (%) = 362 (100, M+).
2
2
4
due was recrystallized from petroleum ether/Et O (2:1); yield:
Anal. calcd for C H N O (362.4): C 82.85, H 5.00, N 7.73; found:
C 82.79, H 4.99, N 7.59.
2
2
5
18
2
6
.11 g (86%); mp 49¡C.
IR (KBr): n = 3050, 3000 (CÐH arom), 2960, 2930, 2860, 2830
Ð1
1
,1'-Dimethoxy-3,3'-biisoquinoline (9)
(CÐH aliph), 1600, 1565, 1495 cm (C=C).
Under nitrogen protection tert-butyl alcohol (3.82 g, 51.5 mmol)
was added dropwise to a suspension of NaH (3.72 g, 155 mmol), an-
hyd NiAc (4.56 g, 25.8 mmol) and Ph P (24.6 g, 93.8 mmol) in eth-
1
H NMR (CDCl , 250 MHz): d = 3.95 (s, 3 H, C3-OCH ), 3.97 (s,
3
3
3
H, C2-OCH ), 7.13 (s, 1 H, H-4), 7.38Ð7.47 (m, 2 H), 7.64Ð7.71
3
2
3
(m, 1 H), 8.10Ð8.17 (m, 1 H).
ylene glycol dimethyl ether (90 mL). The reaction mixture was kept
at 65¡C for 2 h. Then a solution of 8 (5.00 g, 25.8 mmol) in ethylene
glycol dimethyl ether (30 mL) was added and the mixture was
stirred at 65¡C for 3.5 h. After cooling, excess NaH was cautiously
hydrolized with EtOH. The solvent was removed and the oily resi-
due was dissolved in CH Cl . The solution was then filtered with
13
C NMR (CDCl , 63 MHz): d = 55.9 (OCH ), 60.7 (OCH ), 107.1,
3
3
3
1
(
16.4 (quart C), 125.1, 126.0, 126.7, 126.7, 128.0 (quart C), 131.6
quart C), 147.4 (quart C), 152.6 (quart C).
MS (EI, 70 eV): m/z (%) = 266 (100, M ) ref. to 79Br.
+
2
2
Anal. calcd for C H BrO (267.1): C 53.96, H 4.15; found: C
5
12
11
2
CH Cl through a silica gel column (5 cm) and the solvent was
2
2
4.04, H 4.38.
Synthesis 1999, No. 3, 429–434 ISSN 0039-7881 © Thieme Stuttgart · New York