Benzoazocines from Tetrahydroisoquinolines and Activated Alkynes
1
(ethyl acetate/hexane). H NMR (400 MHz, CDCl3): δ = 1.07 (t, J
Methyl 3-Ethyl-6-(4-fluorophenyl)-8,9-dimethoxy-1,2,3,6-tetra-
= 7.2 Hz, 3 H, –CH2–CH3), 2.76–2.87 (m, 3 H, CH2-1 and CH2- hydrobenzo[d]azocine-5-carboxylate (12): Yield 307 mg (77%) in
2), 3.16 (qd, J = 7.2, J = 14.1 Hz, 2 H, –CH2–CH3), 3.49–3.58 (m,
methanol (351 mg, 88% in acetonitrile), white crystals, m.p. 95–
1 H, CH2-2), 3.74 (s, 3 H, OCH3), 3.76 (s, 3 H, OCH3), 3.85 (s, 3 97 °C (ethyl acetate/hexane). 1H NMR (400 MHz, CDCl3): δ = 1.08
H, OCH3), 3.86 (s, 3 H, OCH3), 5.80 (s, 1 H, 6-H), 6.63 (s, 1 H, 7- (t, J = 7.2 Hz, 3 H, –CH2–CH3), 2.74–2.87 (m, 3 H, 2ϫCH2-1 and
H), 6.78–6.80 (m, 3 H, 2ϫCH-Ar and 10-H), 7.02 (d, J = 7.4 Hz,
2 H, 2ϫCH-Ar), 7.68 (s, 1 H, 4-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 15.3, 36.7, 48.6, 51.4, 54.9, 55.7, 55.7 56.0, 97.1, 114.2,
116.2, 116.2, 117.0, 117.1, 127.1, 129.6, 132.4, 139.4, 147.1, 147.5,
CH2-2), 3.13–3.23 (m, 2 H, –CH2–CH3), 3.42–3.50 (m, 1 H, CH2-
2), 3.75 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3),
5.81 (s, 1 H, 6-H), 6.64 (s, 1 H, 7-H), 6.77 (s, 1 H, 10-H), 6.93 (t,
J = 8.7 Hz, 2 H, 2ϫCH-Ar), 7.05–7.12 (m, 2 H, 2ϫCH-Ar), 7.67
152.9, 153.1, 157.5, 170.4 ppm. IR (KBr): ν = 1670, 1577 cm–1. EI
(s, 1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.9, 36.9,
˜
MS: m/z (%) = 411 (20) [M]+, 354 (20), 340 (35), 282 (10), 176 (20), 48.7, 49.0, 51.3, 51.9, 55.9, 56.0, 98.0, 115.0 (d, JC,F = 21 Hz, 2
2
3
164 (50), 151 (20), 135 (14), 121 (60), 91 (15), 72 (40), 58 (100), 56
(50), 42 (30). C24H29NO5 (411.20): calcd. C 70.05, H 7.10, N 3.40;
found C 70.04, H 7.12, N 3.39.
C), 116.0, 116.6, 127.6 (d, JC,F = 7 Hz, 2 C), 128.7, 132.2, 142.8
4
1
(d, JC,F = 3 Hz), 147.0, 147.6, 152.8, 161.0 (d, JC,F = 234 Hz),
170.8 ppm. IR (KBr): ν = 1670, 1605 cm–1. EI MS: m/z (%) = 399
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(72) [M]+, 384 (11), 370 (17), 354 (10), 342 (10), 341 (23), 340 (100),
329 (20), 328 (70), 312 (7), 295 (9), 270 (12), 240 (7), 183 (7), 164
(12), 133 (5), 109 (6), 59 (5). C23H26FNO4 (399.18): calcd. C 69.16,
H 6.56, F 4.76, N 3.51; found C 69.15, H 6.58, F 4.74, N 3.52.
1-[3-Ethyl-8,9-dimethoxy-6-(4-methoxyphenyl)-1,2,3,6-tetrahydro-
benzo[d]azocine-5-yl]ethan-1-one (9): Yield 336 mg (85%) in aceto-
nitrile, white crystals, m.p. 146–147 °C (ethyl acetate/hexane). 1H
NMR (400 Hz, CDCl3): δ = 1.13 (t, J = 7.2 Hz, 3 H, –CH2–CH3),
2.34 (s, 3 H, COCH3), 2.86 (m, 3 H, CH2-1 and CH2-2), 3.22 (dq,
J = 1.5, J = 7.2 Hz, 2 H, –CH2–CH3), 3.60 (m, 1 H, CH2-2), 3.76
(s, 3 H, OCH3), 3.83 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 6.11 (s,
1 H, 6-H), 6.63 (s, 1 H, 7-H), 6.74 (s, 1 H, 10-H), 6.77 (d, J =
8.4 Hz, 2 H, 2ϫCH-Ar), 6.92 (d, J = 8.4 Hz, 2 H, 2ϫCH-Ar),
1-[3-Ethyl-6-(4-fluorophenyl)-8,9-dimethoxy-1,2,3,6-tetrahydro-
benzo[d]azocin-5-yl]ethan-1-one (13): Yield 280 mg (73%) in aceto-
nitrile, white crystals, m.p. 131–132 °C (ethyl acetate/hexane). 1H
NMR (400 MHz, CDCl3): δ = 1.12 (t, J = 7.2 Hz, 3 H, –CH2–
CH3), 2.33 (s, 3 H, COCH3), 2.75–2.91 (m, 3 H, 2ϫCH2-1 and
CH2-2), 3.22 (dq, J = 1.2, J = 7.1 Hz, 2 H, –CH2–CH3), 3.45–3.55
(m, 1 H, CH2-2), 3.82 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 6.12
(s, 1 H, 6-H), 6.62 (s, 1 H, 7-H), 6.72 (s, 1 H, 10-H), 6.70 (t, J =
8.7 Hz, 2 H, 2ϫCH-Ar), 6.94–6.98 (m, 2 H, 2ϫCH-Ar), 7.50 (s,
1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.8, 25.1, 36.6,
7.51 (s, 1 H, 4-H) ppm. IR (KBr): ν = 1610, 1582 cm–1. EI MS:
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m/z (%) = 395 (15) [M]+, 295 (25), 281 (15), 58 (100), 43 (30).
C24H29NO4 (395.21): calcd. C 72.89, H 7.39, N 3.54; found C
72.91, H 7.40, N 3.52.
3-Ethyl-8,9-dimethoxy-6-(4-methoxyphenyl)-5-[(4-methylphenyl)-
sulfonyl]-1,2,3,6-tetrahydrobenzo[d]azocine (10): Yield 157 mg
(31%), white crystals, m.p. 185–186 °C (ethyl acetate/hexane). 1H
NMR (400 MHz, CDCl3): δ = 1.14 (t, J = 7.1 Hz, 3 H, –CH2–
CH3), 2.38 (s, 3 H, CH3–Ar), 2.71 (dd, J = 5.5, J = 15.1 Hz, 1 H,
CH2-1), 2.80–2.88 (m, 2 H, CH2-1 and –CH2–CH3), 3.21–3.27 (m,
2 H, CH2-2 and –CH2–CH3), 3.38 (s, 3 H, OCH3), 3.52–3.62 (m,
1 H, CH2-2), 3.78 (s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 4.89 (s, 1
H, 6-H), 5.57 (s, 1 H, 7-H), 6.58 (s, 1 H, 10-H), 6.78 (d, J = 8.5 Hz,
2 H, 2ϫCH-Ar), 7.18 (d, J = 8.5 Hz, 2 H, 2ϫCH-Ar), 7.23 (d, J
= 7.6 Hz, 2 H, 2ϫCH-Ar), 7.68–7.70 (m, 3 H, 2ϫCH-Ar and 4-
2
46.5, 49.0, 52.1, 55.8, 56.0, 113.2, 114.9, 115.0 (d, JC,F = 21 Hz, 2
3
3
C), 116.7, 127.5 (d, JC,F = 7 Hz, 2 C), 128.5, 132.1, 142 (d, JC,F
1
= 3 Hz), 147.0, 147.6, 154.9, 160.0 (d, JC,F = 240 Hz), 194.4 ppm.
IR (KBr): ν = 1574, 1503 cm–1. EI MS: m/z (%) = 383 (7) [M]+,
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340 (13), 312 (10), 283 (5), 269 (7), 218 (10), 183 (6), 133 (8), 109
(5), 72 (13), 58 (100), 43 (35). C23H26FNO3 (383.45): calcd. C 72.04,
H 6.83, N 3.65; found C 72.12, H 6.52, N 3.60.
3-Ethyl-6-(4-fluorophenyl)-8,9-dimethoxy-5-[(4-methylphenyl)sulfon-
yl]-1,2,3,6-tetrahydrobenzo[d]azocine (14): Yield 208 mg (42%) in
acetonitrile, white crystals, m.p. 201–202 °C (ethyl acetate/hexane).
1H (400 MHz, CDCl3): δ = 1.14 (t, J = 7.2 Hz, 3 H, –CH2–CH3),
2.38 (s, 3 H, CH3–Ar), 2.68 (dd, J = 5.2, J = 14.7 Hz, 1 H, CH2-
1), 2.78–2.88 (m, 2 H, –CH2–CH3 and CH2-1), 3.20–3.28 (m, 2 H,
–CH2–CH3 and CH2-2), 3.40 (s, 3 H, OCH3), 3.42–3.55 (m, 1 H,
CH2-2), 3.83 (s, 3 H, OCH3), 4.92 (s, 1 H, 6-H), 5.62 (s, 1 H, 7-H),
6.58 (s, 1 H, 10-H), 6.92 (t, J = 8.7 Hz, 2 H, 2ϫCH-Ar), 7.22–7.24
(m, 4 H, 4ϫCH-Ar), 7.66–7.69 (m, 3 H, 2ϫCH-Ar and 4-H) ppm.
H) ppm. IR (KBr): ν = 1614 cm–1. EI MS: m/z (%) = 507 (5)
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[M]+, 353 (23), 352 (100), 351 (57), 350 (15), 336 (33), 324 (12), 307
(10), 295 (10), 294 (12), 283 (97), 263 (10), 244 (20), 219 (25), 189
(12), 176 (14), 165 (27), 164 (30), 160 (12), 145 (46), 121 (50), 102
(14), 91 (93), 77 (14), 65 (30), 58 (35), 57 (27), 42 (10). C29H33NO5S
(507.21): calcd. C 68.61, H 6.55, N 2.76; found C 68.75, H 6.47, N
2.80.
Dimethyl 3-Ethyl-8,9-dimethoxy-6-(4-methoxyphenyl)-1,2,3,6-tetra-
hydrobenzo[d]azocine-4,5-dicarboxylate (11): Yield 258 mg (55%) in
methanol (70 % in acetonitrile), white crystals, m.p. 188–190 °C
IR (KBr): ν = 1624 cm–1. EI MS: m/z (%) = 495 (7) [M]+, 341 (23),
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340 (100), 339 (17), 324 (13), 312 (5), 283 (97), 207 (15), 183 (8),
133 (12), 109 (8), 91 (25), 58 (7). C28H30FNO4S (495.60): calcd. C
67.86, H 6.10, N 2.83; found C 67.91, H 6.06, N 2.85.
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(ethyl acetate/hexane). H NMR (400 MHz, CDCl3): δ = 0.88 (t, J
= 7.1 Hz, 3 H, –CH2–CH3), 2.58 (ddd, J = 0.7, J = 5.3, J = 7.0 Hz,
1 H, CH2-1), 2.71–2.81 (m, 2 H, –CH2–CH3 and CH2-1), 2.96 (qd, Dimethyl 3-Ethyl-6-(4-fluorophenyl)-8,9-dimethoxy-1,2,3,6-tetra-
J = 7.2, J = 14.3 Hz, 1 H, –CH2–CH3), 3.19 (ddd, J = 1.8, J = 7.0,
J = 15.1 Hz, 1 H, CH2-2), 3.36–3.44 (m, 1 H, CH2-2), 3.72 (s, 3 H,
hydrobenzo[d]azocine-4,5-dicarboxylate (15): Yield 133 mg (29%),
white crystals, m.p. 132–134 °C (ethyl acetate/hexane). 1H NMR
OCH3), 3.76 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3), 3.87 (s, 3 H, (400 MHz, CDCl3): δ = 0.90 (t, J = 7.1 Hz, 3 H, –CH2–CH3), 2.59
OCH3), 3.90 (s, 3 H, OCH3), 5.82 (s, 1 H, 6-H), 6.60 (s, 1 H, 7-H), (ddd, J = 2.0, J = 5.9, J = 16.0 Hz, 1 H, CH2-1), 2.75–2.87 (m, 2
6.77 (d, J = 8.4 Hz, 2 H, 2ϫCH-Ar), 6.80 (s, 1 H, 10-H), 6.99 (d,
J = 8.4 Hz, 2 H, 2ϫCH-Ar) ppm. 13C NMR (100 MHz, CDCl3):
δ = 13.4, 34.2, 45.6, 50.3, 50.9, 51.6, 53.3, 55.1, 55.8, 55.8, 102.4,
H, –CH2–CH3 and CH2-1), 2.99 (qd, J = 7.1, J = 14.2 Hz, 1 H,
–CH2–CH3), 3.23 (ddd, J = 2.0, J = 7.3, J = 15.1 Hz, 1 H, CH2-
2), 3.30–3.39 (m, 1 H, CH2-2), 3.75 (s, 3 H, OCH3), 3.82 (s, 3 H,
113.4 (2 C), 114.1, 116.6, 127.3 (2 C), 129.6, 131.2, 137.0, 147.0, OCH3), 3.90 (s, 3 H, OCH3), 3.93 (s, 3 H, OCH3), 5.86 (s, 1 H, 6-
147.3, 155.6, 157.5, 167.3, 169.8 ppm. IR (KBr): ν = 1728, 1678, H), 6.63 (s, 1 H, 7-H), 6.83 (s, 1 H, 10-H), 6.94 (d, J = 8.7 Hz, 2
˜
1558 cm–1. EI MS: m/z (%) = 469 (5) [M]+, 410 (10), 398 (100), 382 H, 2ϫCH-Ar), 7.05–7.08 (m, 2 H, 2ϫCH-Ar) ppm. IR (KBr): ν
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(15), 350 (20), 339 (25), 283 (15), 59 (12). C26H31NO7 (469.21):
calcd. C 66.51, H 6.65, N 2.98; found C 66.53, H 6.63, N 3.00.
= 1731, 1683, 1563 cm–1. EI MS: m/z (%) = 457 (29) [M]+, 426 (5),
398 (27), 387 (23), 386 (100), 370 (20), 354 (17), 327 (10), 271 (5),
Eur. J. Org. Chem. 2007, 6106–6117
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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