The Journal of Organic Chemistry
Note
1
05.3 (C12), 56.7 (OCH ), 56.4 (OCH ), 56.1 (OCH ), 55.9
5,6-Dihydroisoquinolino[3,2-a]isoquinolinium Bromide (11).
According to the general procedure, 1,2-bis(bromomethyl)benzene (2,
339.7 mg, 1.29 mmol) was reacted with 1,2,3,4-tetrahydroisoquinoline-
1-carbonitrile (16, 203.1 mg, 1.28 mmol. 1.0 equiv). After 2 h, the
3
3
3
(
OCH ), 54.7 (C6), 26.1 (C5). ESI-MS: m/z (%) = 352.2 (100)
3
+
+
[
M] . ESI-HRMS: calculated for [C H NO ] : m/z = 352.1549,
21 22 4
found: 352.1544.
2
,3-Dimethoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquinolino-
2,1-b]isoquinolin-7-ium Bromide (8). According to the general
procedure, 5,6-bis(bromomethyl)-1,3-benzodioxole (18, 281.4 mg,
.92 mmol) was reacted with 6,7-dimethoxy-1,2,3,4-tetrahydro-
reaction mixture was cooled to room temperature, aq NaHCO (100
3
[
mL) was added, and the mixture was stirred for 30 min and extracted
with cyclohexane (4 × 100 mL), and the aqueous layer was
concentrated in vacuo. The remaining residue was extensively washed
with chloroform and the filtrate was concentrated in vacuo to afford the
title compound (260.1 mg, 0.83 mmol, 65%) as a beige solid, mp 238−
242 °C.
0
isoquinoline-1-carbonitrile (1, 200.0 mg, 0.92 mmol. 1.0 equiv).
After 48 h, trituration with diethyl ether/methanol (1/1) afforded the
title compound (168.4 mg, 0.40 mmol, 44%) as a yellow solid, mp
2
92−293 °C.
IR (ATR): 3420 (s, br), 3033 (m, br), 3002 (m), 1640 (s), 1518
1
IR (ATR): 3400 (w, br), 2980 (w), 1606 (m), 1515 (s), 1460 (s),
(m), 1347 (m), 1213 (w), 1153 (w), 771 (s), 761 (s). H NMR,
1
1
356 (s), 1271 (s), 1247 (s), 1187 (s), 1029 (s). H NMR, COSY
300 MHz, DMSO-d ): δ = 9.50 (s, 1H, H-8), 8.82 (s, 1H, H-14), 7.71
s, 1H, H-9), 7.67 (s, 1H, H-1), 7.55 (s, 1H, H-13), 7.11 (s, 1H, H-4),
.42 (s, 2H, H-11), 4.76 (t, J = 6.3 Hz, 2H, H-6), 3.93 (s, 3H, OCH ),
.87 (s, 3H, OCH ), 3.21 (t, J = 6.3 Hz, 2H, H-5). C NMR, HMBC,
HSQC (75 MHz, DMSO-d ): δ = 156.0 (C OCH O), 151.7
COSY (400 MHz, DMSO-d ): δ = 10.16 (s, 1H, H-8), 9.21 (s, 1H, H-
6
(
13), 8.48 (d, J = 8.2 Hz, 1H, H-9), 8.35 (d, J = 8.3 Hz, 1H, H-12),
8.3−8.27 (m, 1H, Ar-H), 8.24 (pseudo-t, J = 7.4 Hz, 1H, H-11), 8.03
(pseudo-t, J = 7.4 Hz, 1H, H-10), 7.64−7.49 (m, 3H, Ar-H), 4.95 (t, J
6
(
6
3
3
13
13
3
= 6.2 Hz, 2H, H-6), 3.36 (t, J = 6.2 Hz, 2H, H-5). C NMR, HMBC,
6
q
2
HSQC (101 MHz, DMSO-d ): δ = 150.8 (C8), 139.5 (C13a), 138.3
6
(
(
(
(
C OMe), 150.8 (C OCH O), 148.7(C OMe), 145.9 (C8), 138.9
(C12a), 136.8 (C11), 135.3 (C4a), 131.7 (Ar-C), 130.9 (C10), 130.0
(C9), 128.6 (Ar-C), 128.3 (Ar-C), 127.5 (C12), 127.0 (C13b), 126.2
(Ar-C), 125.9 (C8a), 121.4 (C13), 55.2 (C6), 26.3 (C5). ESI-MS: m/
q
q
2
q
C14a), 138.9 (C ), 128.8 (C4a), 123.5 (C ), 118.7 (C14), 118.7
C14b), 111.4 (C4), 108.8 (C1), 103.9 (C9), 103.7 (C11), 102.5
C13), 56.2 (OCH ), 55.9 (OCH ), 54.7 (C6), 26.0 (C5). ESI-MS:
q
q
+
+
3
3
z (%) = 232.1 (100) [M] . ESI-HRMS: calculated for [C H N] : m/
17 14
+
m/z (%) = 336.2 (100) [M] . ESI-HRMS: calculated for
z = 232.1126, found: 232.1125
+
[
C H NO ] : m/z = 336.1236, found: 363.1242.
10,11-Dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquino-
linium Bromide (12). According to the general procedure, 1,2-
bis(bromomethyl)-4,5-dimethoxybenzene (17, 405.6 mg, 1.25 mmol)
was reacted with 1,2,3,4-tetrahydroisoquinoline-1-carbonitrile (16,
200.0 mg, 1.26 mmol. 1.0 equiv). After 4 h, trituration with diethyl
ether/methanol (1/1) afforded the title compound (70.0 mg, 0.19
mmol, 15%) as a yellow solid, mp 240−241 °C.
2
0
18
4
2
,3-Dimethoxy-5,6-dihydrobenzo[g]isoquinolino[2,1-b]-
isoquinolinium Bromide (9). According to the general procedure,
,3-bis(bromomethyl)naphthalene (19, 125.0 mg, 0.40 mmol) was
2
reacted with 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbon-
itrile (1, 87.3 mg, 0.40 mmol. 1.0 equiv). After 48 h, trituration with
acetone afforded the title compound (125.5 mg, 0.30 mmol, 74%) as a
dark orange solid, mp 274−275 °C.
IR (ATR): 3443 (m, br), 3360 (m, br), 3011 (m), 1635 (m), 1606
m), 1517 (m), 1501 (s), 1352 (m), 1279 (m), 748 (s). H NMR,
COSY (400 MHz, DMSO-d ): δ = 10.37 (s, 1H, H-8), 9.27 (s, 1H, H-
), 9.19 (s, 1H, H-15), 8.87 (s, 1H, H-14), 8.41 (d, J = 8.4 Hz, 1H, H-
0), 8.34 (d, J = 8.4 Hz, 1H, H-13), 7.88 (ddd, J = 8.4, 6.7, 1.0 Hz, 1H,
H-12), 7.79 (s, 1H, H-1), 7.79 (ddd, J = 8.4, 6.7, 1.0 Hz, 1H, H-11),
.12 (s, 1H, H-4), 4.95 (t, J = 6.1 Hz, 2H, H-6), 3.97 (s, 3H, OCH ),
.88 (s, 3H, OCH ), 3.29 (t, J = 6.1 Hz, 2H, H-5). C NMR, HMBC,
HSQC (151 MHz, DMSO-d ): δ = 153.9 (C8), 151.4 (C OMe),
48.8 (C OMe), 137.1 (C ), 136.7 (C15a), 132.8 (C9), 132.7 (C ),
32.3 (C ), 131.0 (C12), 129.7 (C10), 128.6 (C13), 128.6 (C ), 128.2
C11), 126.0 (C14), 122.5 (C ), 119.5 (C15), 119.2 (C ),111.3 (C4),
08.7 (C1), 56.2 (OCH ), 55.9 (OCH ), 55.7 (C6), 26.2 (C5). ESI-
MS: m/z (%) = 342.2 (100) [M] . ESI-HRMS: calculated for
IR (ATR): 3394 (m, br), 2986 (w), 2837 (w), 1608 (m), 1491 (s),
1
1429 (s), 1250 (s), 1213 (s), 1159 (s), 929 (s). H NMR, COSY (300
1
(
MHz, CDCl ): δ = 10.79 (s, 1H), 8.41 (s, 1H), 8.01−9.94 (m, 1H),
3
6
7.95 (s, 1H), 7.5 3−7.48 (m, 2H), 7.47 (s, 1H), 7.39−7.33 (m, 1H),
5.12 (t, J = 6.3 Hz, 2H), 4.16 (s, 3H, OCH ), 4.08 (s, 3H, OCH ),
9
1
3
3
3.27 (t, J = 6.3 Hz, 2H). 13C NMR, HMBC, HSQC (75 MHz,
CDCl ): δ = 158.5 (C OMe), 153.2 (C OMe), 146.9 (C8), 138.2
3
q
q
7
3
(C13a), 136.8 (C12a), 134.6 (C4a), 131.9, 128.9 128.8 (3 × Ar-C),
126.9 (C13b), 125.6 (Ar-C), 123.5 (8a), 118.6 (C13), 107.8 (C9),
3
13
3
6
q
105.3 (C12), 57.3, 57.3 (2 × OCH ), 54.6 (C6), 27.7. ESI-MS: m/z
3
+
+
1
(%) = 292.2 (100) [M] . ESI-HRMS: calculated for [C H NO ] :
q
q
q
19 18 2
1
m/z = 292.1338, found: 292.1346
q
q
(
5,6-Dihydro[1,3]dioxolo[4,5-g]isoquinolino[2,1-b]isoquino-
lin-7-ium Bromide (13). According to the general procedure, 5,6-
bis(bromomethyl)-1,3-benzodioxole (18, 385.4 mg, 1.25 mmol) was
reacted with 1,2,3,4-tetrahydroisoquinoline-1-carbonitrile (16, 200.0
mg, 1.26 mmol. 1.0 equiv). After 4 h, trituration with diethyl ether/
methanol (1/1) afforded the title compound (160.2 mg, 0.45 mmol,
36%) as a colorless solid, mp 250−252 °C.
q
q
1
3 3
+
+
[
C H NO ] : m/z = 342.1494, found: 342.1503.
23 20 2
2
,3,6,7,14,15-Hexamethoxy-11,12-dihydrodibenzo[f,h]-
isoquinolino[2,1-b]isoquinolinium Bromide (10). According to
the general procedure, 9,10-bis(bromomethyl)-2,3,6,7-tetramethoxy-
phenanthrene (20, 250.0 mg, 0.52 mmol) was reacted with 6,7-
dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile (1, 112.6 mg,
.52 mmol. 1.0 equiv). After 48 h, trituration with acetone afforded the
title compound (26.0 mg, 0.45 mmol, 86%) as a yellow solid, mp 261−
62 °C.
IR (ATR): 3558 (m, br), 2928 (m, br), 2853 (w), 1606 (m), 1606
m), 1514 (s), 1467 (m), 1429 (m), 1287 (m), 1245 (m). H NMR,
COSY (300 MHz, DMSO-d ): δ = 10.23 (s, 1H, H-9), 9.16 (s, 1H, H-
7), 8.37 (s, 1H), 8.10 (s, 1H, H-1), 8.03 (s, 1H), 7.75 (s, 2H), 7.18 (s,
H), 4.99 (t, J = 5.9 Hz, 2H, H-11), 4.13 (s, 3H, OCH ), 4.09−4.03
m, 9H, 3 × OCH ), 4.02 (s, 3H, OCH ), 3.93 (s, 3H, OCH ), 3.34
t, J = 5.9 Hz, 2H, H-12). C NMR, HMBC, HSQC (151 MHz,
DMSO-d ): δ = 153.5, 152.3, 151.3, 150.0, 149.5, 148.6 (6 × C OMe),
42.6 (C9), 141.4, 138.4, 129.7, 128.4, 124.7, 122.3, 119.7, 119.0,
18.9 (9 × C ), 115.8 (C17), 111.4 (C13), 110.8, 107.8, 105.3, 105.0,
04.8 (5 × Ar-C), 56.6, 56.5, 56.4, 56.3, 56.2, 56.0 (6 × OCH ), 54.4
C11), 26.0 (C12). ESI-MS: m/z (%) = 512.3 (100) [M] . ESI-
HRMS: calculated for [C H NO ] : m/z = 512.2073, found:
12.2083.
28
IR (ATR): 3458 (m), 2972 (w), 1616 (m), 1503 (s), 1437 (s), 1220
1
(s), 1030 (s), 933 (s), 918 (m, sh), 782 (s). H NMR, COSY (300
0
MHz, DMSO-d ): δ = 9.63 (s, 1H, H-8), 8.92 (s, 1H, H-14), 8.34−
6
8.00 (m, 1H, Ar-H), 7.76 (s, 1H, H-9), 7.67 (s, 1H, H-13), 7.60−7.54
(m, 2H, Ar-H), 7.54−7.47 (m, 1H, Ar-H), 6.44 (s, 2H, H-11), 4.82 (t,
2
1
3
J = 6.3 Hz, 2H, H-6), 3.31 (d, J = 6.3 Hz, 2H, H-5). C NMR,
HMBC, HSQC (75 MHz, DMSO-d ): δ = 156.0 (C OCH O), 151.2
1
(
6
q
2
6
(C OCH O), 146.2 (C8), 138.7 (C13a), 138.5 (C14a), 135.1 (C4a),
q 2
1
1
131.5, 128.6, 128.2 (3 × Ar-C), 126.9 (C14b), 125.7 (Ar-C), 124.1
3
(C8a), 119.7 (C14), 104.0 (C9), 103.9 (C11), 103.0 (C13), 54.5
+
(
(
(C6), 26.4 (C5). ESI-MS: m/z (%) = 276.1 (100) [M] . ESI-HRMS:
3
3
3
13
+
calculated for [C H NO ] : m/z = 276.1025, found: 276.1034
18
14
2
6
q
5,6-Dihydrobenzo[g]isoquinolino[2,1-b]isoquinolinium Bro-
mide (14). According to the general procedure, 2,3-bis(bromo-
methyl)naphthalene (19, 125.0 mg, 0.40 mmol) was reacted with
1,2,3,4-tetrahydroisoquinoline-1-carbonitrile (16, 63.3 mg, 0.40 mmol.
1.0 equiv). After 48 h, trituration with acetone afforded the title
compound (43.6 mg, 0.12 mmol, 30%) as an orange solid, mp 232−
233 °C.
1
1
1
q
3
+
(
+
3
1
30
6
5
E
J. Org. Chem. XXXX, XXX, XXX−XXX