Barolo et al.
111.0, 110.7, 56.1, 54.2, 53.8, 52.8, 52.4, 42.8, 42.2, 38.7, 37.7,
28.5, 28.3; mp 129-130 °C; FT-IR (KBr pellet, νmax, cm-1
3392brs, 2949s, 2931s, 2844m, 1686s, 1511m, 1460m, 1274m,
1199m, 1102m, 1032m, 883m, 794m, 504m; HRMS [M + H]+
440.0270 (calcd for C19H19BrClNO4 + H]+, 440.0264).
Isolation and Identification of Products. 1-Hydroxy-2-meth-
oxy-4,5,6a,7-tetrahydro-dibenzo[de,g]quinoline-6-carboxylic acid
methyl ester (11a): The product was identical to an authentic
sample.10b
)
1-(1-Hydroxy-2-methoxy-4,5,6a,7-tetrahydro-dibenzo[de,g]-
quinolin-6-yl)ethanone (11b): Compound 11b was purified by
column chromatography (eluent: dichloromethane/ether gradient
elution). It was recrystallized from chloroform:hexane to give white
1-(2-Bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-3,4-
dihydro-1H-isoquinoline-2-carboxylic acid methyl ester (19c).
The ratio of major to minor rotamers was 63:37. Major: 1H NMR
(500 MHz, CDCl3) δ 7.02 (s, 1H), 6.82 (s, 1H), 6.59 (s, 1H), 6.49
(s, 1H), 5.51 (s, 1H), 5.28 (dd, J ) 4.0, 9.5 Hz, 1H), 4.26 (ddd,
J ) 2.0, 5.5, 12.5 Hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.78 (s, 3H),
3.40-3.20 (m, 2H), 3.32 (s, 3H), 2.95 (dd, J ) 10.0, 14.0 Hz,
1H), 2.86 (ddd, J ) 6.0, 11.0, 16.5 Hz, 1H), 2.61 (dt, J ) 5.0, 15.5
Hz, 1H). Minor: 1H NMR (500 MHz, CDCl3) δ 6.96 (s, 1H), 6.66
(s, 1H), 6.56 (s, 1H), 6.55 (s, 1H), 5.46 (s, 1H), 5.40 (dd, J ) 5.5,
7.5 Hz, 1H), 3.92-3.82 (m, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.75
(s, 3H), 3.63 (s, 3H), 3.40-3.20 (m, 2H), 3.02 (dd, J ) 8.0, 14.0
Hz, 1H), 2.76 (ddd, J ) 5.5, 10.5, 15.5 Hz, 1H), 2.54 (dt, J ) 7.0,
16.0 Hz, 1H); 13C NMR (100.5 MHz, CDCl3) δ 156.2, 148.4, 148.3,
148.2, 148.0, 145.7, 145.6, 144.2, 144.1, 130.0, 129.7, 129.3, 129.2,
126.0, 115.4, 115.3, 115.2, 115.1, 114.2, 113.9, 113.3, 112.9, 110.9,
110.6, 56.4, 56.3, 56.1, 54.7, 54.4, 52.8, 52.4, 42.3, 41.4, 39.0, 37.8,
28.4; mp 158-160 °C; FT-IR (KBr pellet, νmax, cm-1) 3366brs,
3000s, 2936s, 2843m, 1684s, 1510s, 1460s, 1261s, 1162m, 1104m,
1029m, 993m, 870m, 764m, 571m; HRMS [M + H]+ 466.0851
(calcd for C12H24BrNO6 + H]+, 466.0865).
1
crystals; mp 260-262 °C (dec). H NMR (CD3SOCD3): δ 8.77
(brs, 1H), 8.40 (d, J ) 7.7 Hz, 1H), 7.29-7.20 (cplx m, 3H), 6.80
(s, 1H), 4.85-4.49 (m, 1H), 4.06-4.00 (m, 1H), 3.84 (s, 3H), 3.19-
3.13 (m, 1H), 2.87-2.63 (cplx m, 4H), 2.12 (s, 3H). 13C NMR
(CD3SOCD3): δ 168.4, 146.7, 142.4, 136.3, 132.1, 128.6, 128.0,
126.7, 126.2, 125.7, 123.9, 119.8, 110.8, 56.0, 49.6, 41.4, 33.8,
29.7, 22.2. EM, m/z (%): 310 (10), 309 (44), 251 (6), 250 (18),
238 (26), 237 (100), 235 (6), 223 (8), 194 (9), 152 (6). HRMS
(EI) calcd for C19H19NO3: 309.1365. Found: 309.1369.
2-Methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]-
quinolin-1-ol (11d): Compound 11d was purified by column
chromatography (eluent: dichloromethane/ether gradient elution).
It was recrystallized from benzene to give white crystals; mp 163-
1
165 °C dec (lit35 167-169 °C). H NMR (CD3COCD3): δ 8.44-
8.39 (cplx m, 1H), 7.57 (brs, 1H), 7.35-7.12 (cplx m, 3H), 6.69
(s, 1H), 3.87 (s, 3H), 3.18-2.87 (cplx m, 4H), 2.65-2.33 (cplx m,
3H), 2.48 (s, 3H). 13C NMR (CD3COCD3): δ 147.5, 143.1, 137.3,
133.9, 129.6, 129.2, 128.7, 127.6, 127.3, 124.9, 120.4, 111.2, 63.8,
56.7, 54.5, 44.5, 36.1. EM, m/z (%): 282 (16), 281(84), 280 (100);
279 (58); 266 (20); 265 (21); 264 (36); 238 (36); 237 (10); 234
(11); 220 (18), 207 (10), 206 (19), 165 (16), 139 (10), 124 (16),
109 (22).
1-[2-(2-Bromophenyl)ethyl]-7-hydroxy-6-methoxy-3,4-dihy-
dro-1H-isoquinoline-2-carboxylic acid methyl ester (24). The
ratio of major to minor rotamers was 55:45. Major: 1H NMR (500
MHz, CDCl3) δ 7.54-7.46 (m, 1H), 7.30-7.18 (m, 2H), 7.07-
7.00 (m, 1H), 6.67 (s, 1H), 6.57 (s, 1H), 5.47 (s, 1H), 5.10-5.03
(m, 1H), 4.33-4.24 (m, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.42-
3.25 (m, 1H), 3.00-2.75 (m, 3H), 2.65 (t, J ) 4.0 Hz, 1H), 2.16-
1.90 (m, 2H). Minor: 1H NMR (500 MHz, CDCl3) δ 7.54-7.46
(m, 1H), 7.30-7.18 (m, 2H), 7.07-7.00 (m, 1H), 6.67 (s, 1H),
6.55 (s, 1H), 5.45 (s, 1H), 5.26-5.19 (m, 1H), 4.12-4.03 (m, 1H),
3.85 (s, 3H), 3.75 (s, 3H), 3.42-3.25 (m, 1H), 3.00-2.75 (m, 3H),
2.62 (t, J ) 3.0 Hz, 1H), 2.16-1.90 (m, 2H); 13C NMR (100.5
MHz, CDCl3) δ 156.6, 145.6, 144.1, 141.5, 141.2, 133.1, 133.0,
132.9, 130.7, 130.5, 130.3, 130.1, 127.8, 127.7, 125.6, 125.3, 124.5,
124.0, 113.1, 112.8, 111.1, 110.9, 56.1, 54.5, 52.9, 38.3, 37.8, 37.0,
1-Benzyl-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol (15):36
Compound 15 was purified by column chromatography (eluent:
petroleum ether (60-80 °C)/acetone gradient elution). It was
recrystallized from benzene to give pale yellow crystals. 1H NMR
(CD3SOCD3): δ 8.52 (brs, 1H), 7.33-7.13 (m, 5H), 6.63 (s, 1H),
6.55 (s, 1H), 3.92-3.89 (m, 1H), 3.69 (s, 3H), 3.25 (brs, 1H), 3.04-
2.96 (m, 2H), 2.76-2.64 (m, 2H), 2.54-2.52 (m, overlapped, 2H).
13C NMR (CD3SOCD3): δ 145.9, 144.2, 139.8, 131.3, 129.3, 128.0,
125.8, 125.6, 113.3, 112.3, 56.1, 55.6, 42.1, 40.0, 29.0. EM, m/z
(%): 266 (8), 179 (12), 178 (100), 163 (19), 134 (6), 91 (8), 65
(5). Compound 15 exhibited spectral and analytical data in
agreement with ref 36.
1-Benzyl-6-methoxyisoquinolin-7-ol (16): Compound 16 was
purified by column chromatography (eluent: petroleum ether (60-
80 °C)/acetone gradient elution). It was recrystallized from benzene
to give white crystals; mp 205-207 °C (lit37 210-212 °C). 1H NMR
(CD3SOCD3): δ 9.81 (brs, 1H), 8.19 (d, J ) 5.5 Hz, 1H), 7.50 (d,
J ) 5.5 Hz, 1H), 7.43 (s, 1H), 7.29-7.09 (cplx m, 6H), 4.43 (s,
2H), 3.91 (s, 3H).13C NMR (CD3SOCD3): δ 156.7, 152.0, 147.7,
139.7, 139.7, 132.1, 128.4, 128.3, 125.9, 122.7, 118.5, 107.3, 105.7,
55.6, 41.1. EM, m/z (%): 266 (5), 265 (36), 264 (100), 249 (13),
248 (8), 221 (6), 220 (5), 204 (7), 102 (8), 96 (6), 51(5).
10-Fluoro-1-hydroxy-2-methoxy-4,5,6a,7-tetrahydrodibenzo-
[de,g]quinoline-6-carboxylic acid methyl ester (20a): Compound
20a was purified by chromatography on silica gel (eluted: petro-
leum ether (60-80 °C)/dichloromethane gradient elution). It was
recrystallized from dichloromethane/petroleum ether as white
crystals; mp 183-184 °C. 1H NMR (CDCl3): δ 8.20 (dd, J ) 11.5,
2.8 Hz, 1H), 7.21 (dd, J ) 8.2, 6.0 Hz, overlapped, 1H), 6.92 (ddd,
J ) 8.4, 8.2, 2.8 Hz, 1H), 6.64 (s, 1H), 6.22 (s, 1H), 4.76 (dd, J )
13.5, 4.0 Hz, 1H), 4.43 (m, 1H), 3.93 (s, 3H), 3.77 (s, 3H), 3.05-
2.56 (cplx m, 5H). 13C NMR (CDCl3): δ 164.1, 159.3, 155.9, 145.7,
142.1, 133.4 (d, JC-F ) 8.1 Hz, 1C), 131.9 (d, JC-F ) 2.7 Hz, 1C),
33.6, 28.3, 28.0; mp 58-59 °C; FT-IR (KBr pellet, νmax, cm-1
)
3369brs, 3007s, 2953s, 2841m, 1693s, 1514s, 1471s, 1448s, 1266s,
1204s, 1099m, 1022m, 752m, 657m, 554m; HRMS [M + H]+
420.0810 (calcd for C20H22BrNO4 + H]+, 420.0811).
Photostimulated Reaction of 1-(2-Bromobenzyl)-7-hydroxy-
6-methoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid meth-
yl ester (10a) with t-BuOK in Liquid Ammonia. The following
procedure is representative. Into a three-necked, 250 mL, round-
bottomed flask equipped with a cold-finger condenser charged with
dry ice-ethanol, a nitrogen inlet, and a magnetic stirrer was
condensed 150 mL of ammonia previously dried with Na metal
under nitrogen. The t-BuOK (1.00 mmol) and 10a (0.50 mmol)
were added, and the mixture was irradiated for 180 min. The
reaction was quenched by addition of NH4NO3 in excess, and the
ammonia was allowed to evaporate. The residue was dissolved with
water (60 mL) and then extracted with methylene chloride (3 ×
20 mL), and the organic extract was washed twice with water
(2 × 20 mL) and dried over anhydrous Na2SO4. The bromide ions
in the aqueous solution were determined potentiometrically. The
product 11a was purified by column chromatography and quantified
by GLC using the internal standard method.
Reaction of 10a with t-BuOK in Liquid Ammonia in the
Dark. The procedure was similar to that for the previous reaction,
except that the reaction flask was wrapped with aluminum foil.
Inhibited Photostimulated Reaction of 10a with t-BuOK in
Liquid Ammonia. The procedure was similar to that for the
previous reaction, except that p-DNB (20 mol %) was added to
the solution.
(35) Gilbert, B. B.; Gilbert, M. E. A.; De Oliveira, M. M.; Ribeiro, O.;
Wenkert, E.; Wickberg, B.; Hollstein, U.; Rapoport, H. J. Am. Chem. Soc.
1964, 86, 694-696.
(36) Bobbitt, J. M.; Cheng, T. Y. J. Org. Chem. 1976, 41, 443-449.
(37) Kratzl, K.; Billet, G. Monatsh 1952, 83, 1409-1417.
8498 J. Org. Chem., Vol. 71, No. 22, 2006