(1Í, m, Í -10), 3.67 (3Í, s, 7-ÎÑÍ ), 3.65–3.70 (1Í, m, Í -10), 3.74* (3Í, s, 3ꢂ-ÎÑÍ ), 3.87* (3Í, s, 6-ÎÑÍ ), 3.94* (3Í,
å
3
à
3
3
s, 4ꢂ-ÎÑÍ ), 5.4 (1Í, s, Í-1), 6.33 (1Í, s, Í-8), 6.62 (1Í, s, Í-5), 6.69 (1H, s, H-2ꢂ), 7.37 (1Í, s, Í-5ꢂ).
3
1-(3ꢂ,4ꢂ-Methylenedioxyphenyl)-2ꢁ-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (5g).
C H NO . Method B. Prepared as the hydrochloride from 4g (1.5 g, 0.005 mol), ethylenechlorohydrin (0.9 mL, 0.013 mol),
20 23
5
and K CO (0.8 g, 0.006 mol). Yield 1.34 g (78%), mp of hydrochloride 149–152°C (Me CO), R 0.71 (system 3).
2
3
2
f
PMR spectrum (400 ÌHz, CDÑl , ꢃ, ppm, J/Hz): 2.56 (1Í, dt, J = 4.4, 4.4, 12.9, Í -9), 2.67 (1Í, ddd, J = 4.6, 9.0,
3
e
12.0, Í -3), 2.77 (1Í, ddd, J = 5.4, 9.0, 16.0, Í -4), 2.90 (1Í, ddd, J = 4.4, 8.3, 12.9, Í -9), 2.96 (1Í, dt, J = 5.3, 5.3, 16.0,
a
e
à
Í -4), 3.19 (1H, dt, J = 5.5, 5.5, 12.0, H -3), 3.48 (1Í, ddd, J = 4.4, 9.4, 11.1, Í -10), 3.58 (3Í, s, 7-ÎÑÍ ), 3.64 (1Í, ddd,
a
e
å
3
J = 4.4, 8.3, 11.1, Í -10), 3.78 (3Í, s, 6-ÎÑÍ ), 4.57 (1Í, s, Í-1), 5.85, 5.86 (each 1Í, d, J = 1.5, 3ꢂ-ÎÑÍ Î-4ꢂ), 6.17 (1Í, s,
à
3
2
Í-8), 6.55 (1Í, s, Í-5), 6.63 (1Í, s, Í-6ꢂ), 6.67 (1Í, s, Í-5ꢂ), 6.67 (1Í, s, Í-2ꢂ).
1-(6ꢂ-Bromo-3ꢂ,4ꢂ-methylenedioxyphenyl)-2ꢁ-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (5h).
C H BrNO . Method B. Prepared from 4h (1.5 g, 0.004 mol), ethylenechlorohydrin (0.78 mL, 0.012 mol), and K CO
3
20 22
5
2
–1
(0.8 g, 0.006 mol). Yield 1.17 g (77%), mp 143–144°C (MeOH), R 0.87 (system 2). IR spectrum (KBr, ꢄ , cm ): 3425
f
max
(ÎÍ), 1610 (C=C), 1515 (Ar–H), 1476 (CH ), 1251, 1225 (C–O), 1131 (C–N), 1040 (C–Br), 939, 928 (O–CH –O), 859, 804.
2
2
PMR spectrum (400 ÌHz, CDÑl , ꢃ, ppm, J/Hz): 2.47 (1Í, dt, J = 3.5, 3.5, 12.7, Í -9), 2.58 (1Í, ddd, J = 4.0, 9.5,
3
e
12,0, Í -3), 2.69 (1Í, dt, J = 4.6, 4.2, 16.0, Í -4), 2.76 (1Í, ddd, J = 4.8, 9.8, 12.8, Í -9), 2.92 (1Í, ddd, J = 4.6, 9.5, 15.5,
a
e
à
Í -4), 3.16 (1H, dt, J = 4.5, 4.5, 11.8, H -3), 3.39 (1Í, ddd, J = 3.6, 4.8, 11.0, Í -10), 3.61 (3Í, s, 7-ÎÑÍ ), 3.64 (1Í, ddd,
a
e
å
3
J = 3.5, 9.8, 11.0, Í -10), 3.79 (3Í, s, 6-ÎÑÍ ), 4.99 (1Í, s, Í-1), 5.86 (2Í, s, 3ꢂ-ÎÑÍ Î-4ꢂ), 6.16 (1Í, s, Í-8), 6.50 (1Í, s,
à
3
2
Í-2ꢂ), 6.54 (1Í, s, Í-5), 6.95 (1Í, s, Í-5ꢂ).
1-(6ꢂ-Chloro-3ꢂ,4ꢂ-methylenedioxyphenyl)-2ꢁ-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (5i).
C H ClNO . Method B. Prepared from 4i (1.5 g, 0.004 mol), ethylenechlorohydrin (0.9 mL, 0.013 mol), and K CO
20 22
5
2
3
–1
(0.8 g, 0.006 mol). Yield 1.46 g (87%), mp 157–159°C (MeOH), R 0.92 (system 2). IR spectrum (KBr, ꢄ , cm ): 3503
f
max
(ÎÍ), 1613 (C=C), 1505 (Ar–H), 1474 (CH ), 1248, 1225 (C–O), 1128 (C–N), 1033 (C–Cl), 929 (O–CH –O), 877, 859.
2
2
–1
IR spectrum in vaseline oil (ꢄ , cm ): 3501 (ÎÍ free), 3159 (intramolecular H-bond), 1611 (C=C), 1499 (Ar–H),
max
1306, 1222 (C–O), 1127 (C–N), 1032 (C–Cl), 928 (O–CH –O).
2
PMR spectrum (400 ÌHz, CDÑl , ꢃ, ppm, J/Hz): 2.49 (1Í, dt, J = 3.7, 13.0, Í -9), 2.58 (1Í, ddd, J = 4.1, 9.3, 12,1,
3
e
Í -3), 2.70 (1Í, dt, J = 4.1, 5.1, 15.7, Í -4), 2.73 (1Í, ddd, J = 4.9, 9.6, 13.0, Í -9), 2.89 (1Í, ddd, J = 5.1, 9.3, 15.7, Í -4),
a
e
à
a
3.15 (1H, dt, J = 5.1, 5.1, 12.1, H -3), 3.41 (1Í, ddd, J = 3.7, 4.9, 11.1, Í -10), 3.61 (3Í, s, 7-ÎÑÍ ), 3.63 (1Í, ddd, J = 3.7,
e
å
3
9.6, 11.1, Í -10), 3.79 (3Í, s, 6-ÎÑÍ ), 5.02 (1Í, s, Í-1), 5.86 (2Í, s, 3ꢂ-ÎÑÍ Î-4ꢂ), 6.14 (1Í, s, Í-8), 6.47 (1Í, s, Í-2ꢂ), 6.54
à
3
2
(1Í, s, Í-5), 6.78 (1Í, s, Í-5ꢂ).
3,11,12-Trimethoxy-6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinolin-2-ol (7). C H NO . Method A.
20 23
4
Prepared as the hydrochloride from 6 (2.0 g, 0.006 mol), ethylenechlorohydrin (1 mL, 0.015 mol), and KOH (0.37 g). Yield
1.93 g (85%).
Method B. Prepared from 6 (1.0 g, 0.003 mol), ethylenechlorohydrin (0.7 mL, 0.01 mol), and K CO (1.85 g,
2
3
0.013 mol) as the hydrochloride. Yield 0.6 g (53%), mp of hydrochloride 188–191°C, R 0.59 (system 2).
f
PMR spectrum (400 ÌHz, CD OD, ꢃ, ppm, J/Hz): 2.557 (1Í, br.td, J = 13.2, 6.5, H-9a), 2.68–2.78 (3Í, m, Í-9å, 6à,
3
5à), 2.992 (1Í, ddd, J = 15.7, 10.2, 6.2, Í-6å), 3.248 (1Í, d, Í-5å), 3.508 (3Í, s, 12-ÎÑÍ ), 3.581 (2Í, m, Í-8), 3.731* (3Í,
3
s, 11-ÎÑÍ ), 3.788 (3Í, s, 3-ÎÑÍ ), 5.046 (1Í, br.s, Í-13b), 6.163 (1Í, s, Í-13), 6.569 (1Í, s, Í-1), 6.653 (1Í, s, Í-10),
3
3
7.064 (1Í, s, H-4).
REFERENCES
th
1.
2.
M. D. Mashkovskii, Drugs [in Russian], Vol 1, 13 Ed., Ibn Sino, Tashkent, 1998.
H. Ott, G. E. Hardtmann, M. Denzer, A. J. Frey, J. H. Gogerty, G. H. Leslie, and J. H. Trapold, J. Med. Chem.,
11, 777 (1968).
3.
4.
K. T. Wanner, H. Beer, G. Hofner, and M. Ludwig, Eur. J. Org. Chem., 9, 2019 (1998).
F. M. Tursunkhodzhaeva, Sh. B. Rakhimov, F. N. Dzhakhangirov, V. I. Vinogradova, Zh. Rezhepov,
and Sh. Sh. Sagdullaev, UzIAP 04590, 2012.
5.
6.
Sh. N. Zhurakulov, V. I. Vinogradova, and M. G. Levkovich, Chem. Nat. Compd., 49, 70 (2013).
L. Zhelyazkov and S. Zikolova, Tr. VNIKhFI, 9, 9 (1959).
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