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A. Głuszynska et al. / Tetrahedron: Asymmetry 15 (2004) 2499–2505
2504
phase was washed with water, dried and the solvent
evaporated. The residue (92%) was dissolved in 96% eth-
anol and treated at ice-bath temperature with 4.8% tet-
rafluoroboric acid (from aqueous 48% HBF4 and
ethanol) to reach pH ca. 1. Fine crystals of tetrafluoro-
3288, 1662. 1H NMR (CDCl3/D2O) d: 2.44 (s, 3H, SCH3),
3.80 (s, 3H, N+CH3), 3.96 (2ABq, J = 5.2, 5.5, 12.1Hz,
2H, CH2O), 4.24 (t, J = ca. 5Hz, 1H, H-3), 4.48 (s, 1H,
H-4), 6.81 (d, J = 8.2Hz, 2H, Ar-H), 7.16 (m, 2H, Ar-
H), 7.31 (d, J = 7.7Hz, 1H, Ar-H), 7.57 (dq, J = 1.1,
7.4Hz, 1H, H-7), 7.77 (dq, J = 1.1, 7.7Hz, 1H, H-6),
8.00 (d, J = 7.7Hz, 1H, H-8), 9.09 (s, 1H, H-1). 13C
NMR (DMSO-d6) d: 14.51 (SCH3), 41.65 (CH), 47.47
(NCH3), 60.89 (CH2), 68.19 (CH), 123.66 (CH), 126.30
(2CH), 127.92 (2CH), 128.62 (CH), 129.49 (CH), 133.53
(CH), 137.46 (C), 137.60 (C), 137.79 (C), 138.20 (C),
167.48 (CH). EI MS m/z (%): 298 (M+, 6), 297 (M+ꢀ1,
26), 267 (30), 254 (12), 224 (33), 194 (65), 173 (59), 165
(32), 144 (100). Anal. Calcd for C18H20BF4NOSÆ1/4
H2O (389.43): C, 55.47; H, 5.31; N, 3.59; S, 8.21. Found:
C, 55.79; H, 5.70; N, 3.44; S, 8.15.
borate salt
2
were collected, mp 61.5–63.5°C,
[a]D = ꢀ148.3 (c 1, chloroform), lit.2 mp 50–58°C,
[a]D = +148.0 (c 1.25, chloroform). IR (KBr), m (cmꢀ1):
3424 (br), 1663 (C@N+). H NMR (CDCl3) d: 1.54 (d,
1
J = 6.9Hz, 3H, CCH3), 3.73 (d, J = 0.8Hz, 3H,
N+CH3), 4.29 (dq, J = 2.9, 6.9Hz, 1H, H-3), 4.35 (d,
J = 2.9Hz, 1H, H-4), 6.91 (m, 2H, Ar-H), 7.24 (m, 4H,
Ar-H), 7.57 (dt, J = 1.2, 7.7Hz, 1H, H-7), 7.76 (dt,
J = 1.4, 7.8Hz, 1H, H-6), 8.09 (dd, J = 1.4, 7.7Hz, 1H,
H-8), 9.25 (s, 1H, H-1). 13C NMR (CDCl3) d: 17.18
(CH3), 46.67 (NCH3), 47.89 (CH), 64.53 (CH), 124.04
(C), 127.28 (2CH), 128.32 (CH), 129.45 (CH), 129.50
(2CH), 129.88 (CH), 134.79 (CH), 136.38 (C), 138.76
(CH), 139.05 (C), 166.93 (CH). MS m/z (%): 237
(M++1ꢀBF4, 18), 237 (M+ꢀBF4, 18), 180 (52), 179
(100), 178 (98), 165 (25), 142 (18), 115 (11). Anal. Calcd
for C17H18NBF4Æ1H2O: C, 59.85; H, 5.91; N, 4.11.
Found: C, 59.74; H, 5.68; N, 4.28.
4.3.2. From dihydroisoquinoline 11.
4.3.2.1. (3R,4R)-3-Hydroxymethyl-4-(4-methylthio-
phenyl)-3,4-dihydroisoquinoline 17. Tetrahydroiso-
.
quinoline 11 (3.46g, 12.1mmol), iodine (10.9g,
42.9mmol) and sodium acetate (3.64g, 44mmol) in
96% ethanol (120mL) were heated at reflux for 1h.
The solvent was then evaporated and the residue dis-
solved in methylene chloride and washed with satd
sodium thiosulfate, 5% sodium hydroxide and water.
After the standard work-up of the organic phase, the
oily product, obtained in quantitative yield, was crystal-
lized from 96% ethanol and then from acetone to give
crystalline 17, mp 127–130°C, [a]D = ꢀ100.4 (c 0.56,
methanol), [a]D = +64.4 (c 0.25, chloroform).
4.3. (3R,4R)-3-Hydroxymethyl-2-methyl-4-(4-methylthio-
phenyl)-3,4-dihydroisoquinolinium tetrafluoroborate 16
4.3.1. From N-methyltetrahydroisoquinoline 12. Tetra-
hydroisoquinoline 12 (0.15g, 0.5mmol), iodine (0.76g,
3mmol) and sodium acetate (0.26g, 3.2mmol) in 96%
ethanol (5mL) were heated at reflux until no more start-
ing material was present (TLC). The solvent was evapo-
rated and the residue dissolved in methylene chloride,
washed with satd sodium thiosulfate and water. After
the standard work-up unstable iodide, 16a, was ob-
tained as a yellow oil (0.16g, 73%) and directly trans-
formed into the tetrafluoroborate 16. A sample of the
iodide 16a was characterized: IR (KBr), m (cmꢀ1):
1
IR (KBr), m (cmꢀ1): 3237, 1625. H NMR (CDCl3) d:
2.51 (s, 3H, SCH3), 3.30 (br s, disappeared on treatment
with D2O, OH), 3.48 (m, 1H, CHH), 3.84 (m, 2H, H-3,
CHH), 4.02 (d, J = 14.0Hz, 1H, H-4), 6.77 (m, 1H, Ar-
H), 7.15–7.39 (m, 6H, Ar-H), 8.44 (d, J = 2.5Hz, 1H, H-
1). 13C NMR (CDCl3) d: 15.79 (CH3), 43.22 (CH2),
64.19 (CH), 64.28 (CH), 127.02 (2CH), 127.28 (CH),
127.41 (CH), 127.45 (CH), 127.91 (CH), 129.83 (2CH),
131.80 (CH), 137.26 (2C), 137.35 (C), 139.45 (C),
160.63 (CH). EI MS m/z (%): 283 (M+, 100), 266 (74),
252 (32), 224 (31), 204 (16), 179 (19), 178 (59), 165
(24), 130 (24). HRMS calcd for C17H17NOS
283.10299. Found 283.10309.
1
3284, 1660. H NMR (CDCl3) d: 2.43 (s, 3H, SCH3),
3.83 (s, 3H, N+CH3), 3.98 (dd, J = 4.74, 12.4Hz, 1H,
CHH), 4.12 (dd, J = ca. 7, 12.4Hz, 1H, CHH), 4.25
(m, 2H, H-3, OH), 4.57 (s, 1H, H-4), 6.88 (d,
J = 8.5Hz, 2H, Ar-H), 7.16 (d, J = 8.5Hz, 2H, Ar-H),
7.34 (d, J = 7.7Hz, 1H, H-5), 7.54 (m, 1H, H-7), 7.74
(m, 1H, H-6), 8.17 (d, J = 6.9Hz, 1H, H-8), 9.79 (s,
1H, H-1). MS m/z (%): 423 (M+ꢀ2, 1), 298 (M+ꢀI,
14), 297 (M+ꢀ1, ꢀI, 37), 283 (22), 281 (13), 280 (12),
268 (79), 267 (41), 266 (35), 224 (45), 194 (68), 193
(14), 179 (23), 178 (25), 174 (10), 173 (79), 165 (28),
144 (100), 142 (24), 137 (13). HRMS of (M+ꢀ2) calcd
for C18H18NOSI 423.01528. Found 423.01538.
4.3.2.2.
methylthiophenyl)-3,4-dihydroisoquinolinium
(3R,4R)-3-Hydroxymethyl-2-methyl-4-(4-
tetrafluo-
roborate 16. Compound 17 (0.529g, 1.87mmol) was
dissolved in methyl iodide (4mL) and left at rt for 6h.
Then the excess of methyl iodide was removed, and
the oily residue crystallized two times from 96% ethanol
to give 0.55g (69%) of iodide 16a, identical to that pre-
pared by the oxidation of N-methyltetrahydroisoquino-
line 12. It was then transformed into the
tetrafluoroborate salt 16 following the above procedure
(Section 4.3.1).
4.3.1.1. Tetrafluoroborate, 16. Iminium iodide 16a
(0.733g, 1.72mmol) in ethanol (10mL) was treated with
5% sodium hydroxide. Then alcohol was evaporated
under reduced pressure and the residue extracted with
methylene chloride. The organic phase was washed with
water and the solvent evaporated. The residue was dis-
solved in ethanol again and treated with 4.8% tetrafluo-
roboric acid to pH ca. 1, to deposit 0.508g (76%) of
crystalline 16; mp 123–128°C (from 96% ethanol/hexane),
[a]D = ꢀ285.2 (c 0.5, methanol). IR (KBr), m (cmꢀ1): 3509,
Acknowledgements
This work was supported by a research grant from the
State Committee for Scientific Research in the year
2003–2006 (KBN Grant no 4T09A 07824).