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D. Collado et al. / Tetrahedron 62 (2006) 2927–2935
4.2.3. 3-Methoxy-4-tosysloxy-benzylchloride (24). Pre-
pared by using the above-described procedure for 21. White
solid; mpZ110–112 8C (AcOEt); yield 86%; 1H NMR
(CDCl3) d 2.43 (s, 3H), 3.57 (s, 3H), 4.50 (s, 2H), 6.85–6.89
(m, 2H), 7.08 (d, 1H, JZ9.1 Hz), 7.28 (d, 2H, JZ7.9 Hz),
7.74 (d, 2H, JZ7.9 Hz); 13C NMR (CDCl3) d 21.5, 45.5,
55.5, 112.8, 120.5, 123.9, 128.4, 129.3, 133.0, 137.4, 138.1,
145.1, 151.8; MS m/z (%) 326 (6) [M]C, 91 (100), 65 (66).
Anal. Calcd for C15H15O4ClS: C, 55.13; H, 4.63. Found: C,
55.14; H, 4.65.
by column chromatography. When necessary, mixtures of
regioisomeric phenols were further separated by preparative
TLC.
4.3.1. 1-(3,4-Dihydroxybenzyl)isoquinoline (6). See
Ref. 30.
4.3.2. 1-(2,4-Dihydroxy-5-methoxybenzyl)isoquinoline
(8). Oil; yield 35%; 1H NMR (CDCl3) d 3.81 (s, 3H),
4.48 (s, 2H), 6.60 (s, 1H), 6.77 (s, 1H), 7.55 (d, 1H, JZ
6.1 Hz), 7.64–7.76 (m, 2H), 7.83 (d, 1H, JZ7.9 Hz), 8.34
(d, 1H, JZ6.1 Hz), 8.40 (d, 1H, JZ7.3 Hz); 13C NMR
(CDCl3) d 31.2, 55.8, 111.9, 114.6, 120.9, 122.8, 124.3,
127.4, 128.3, 128.6, 128.8, 129.5, 129.6, 136.1, 144.5,
146.9, 147.9; MS m/z (%) 281 (100) [M]C, 168 (72), 167
(79); HRMS (FAB) m/z calcd for C17H15NO3
(M)C281.1052, found 281.1060.
4.2.4. 1-(3-Methoxy-4-hydroxybenzyl)isoquinoline (10).
Prepared by using the above-described procedure for 7.
White solid; mpZ139–140 8C (AcOEt); yield 73%; 1H
NMR (CDCl3) d 3.70 (s, 3H), 4.57 (s, 2H), 6.77–6.79
(m, 3H), 7.48–7.59 (m, 3H), 7.79 (d, 1H, JZ8.5 Hz), 8.16
(d, 1H, JZ8.5 Hz), 8.47 (d, 1H, JZ6.1 Hz); 13C NMR
(CDCl3) d 41.6, 55.7, 111.3, 114.4, 119.8, 121.3, 125.8,
127.1, 127.3, 129.2, 129.9, 131.2, 136.6, 141.8, 144.2,
146.7, 160.4; MS m/z (%). Anal. Calcd for C17H15NO2:
C, 76.96; H, 5.70; N, 5.28. Found: C, 76.98; H, 5.73; N,
5.29.
4.3.3. 1-(2,4-Dihydroxy-3-methoxybenzyl)isoquinoline
(9). Oil; yield 13%; H NMR (CDCl3) d 3.98 (s, 3H), 4.51
1
(s, 2H), 6.41 (d, 1H, JZ8.5 Hz), 6.91 (d, 1H, JZ8.5 Hz),
7.56 (d, 1H, JZ5.5 Hz), 7.68–7.76 (m, 2H), 7.83 (d, 1H, JZ
6.7 Hz), 8.34 (d, 1H, JZ6.1 Hz), 8.40 (d, 1H, JZ8.5 Hz);
13C NMR (CDCl3) d 36.2, 57.4, 111.4, 122.7, 123.6, 125.2,
125.8, 126.8, 128.6, 129.0, 131.6, 136.5, 136.6, 140.9,
145.9, 148.1, 158.3; MS m/z (%) 281 (100) [M]C, 168 (72),
167 (79); HRMS (FAB) m/z calcd for C17H15NO3
(M)C281.1052; found 281.1056.
4.2.5.
1-(3-Methoxy-4-hydroxybenzyl)isoquinoline
N-oxide (3). An amount of 0.8 g (3.0 mmol) of 1-(3-
methoxy-4-hydroxybenzyl)isoquinoline was reacted as for
the preparation of 1. White solid; mpZ204–205 8C
1
(AcOEt); yield 73%; H NMR (CDCl3) d 3.81 (s, 3H),
4.55 (s, 2H), 5.60 (s, 1H), 6.74 (s, 2H), 7.04 (s, 1H), 7.50–
7.64 (m, 3H), 7.76 (d, 1H, JZ7.9 Hz), 8.02 (d, 1H, JZ
7.9 Hz), 8.20 (d, 1H, JZ6.7 Hz); 13C NMR (CDCl3) d 31.2,
55.8, 111.9, 114.6, 120.5, 121.0, 122.5, 124.1, 127.3, 128.7,
129.2, 129.3, 136.6, 144.7, 147.0, 147.5; MS m/z (%) 281
(13) [M]C, 280 (20), 264 (100). Anal. Calcd for
C17H15NO3: C, 76.96; H, 5.70; N, 5.28. Found: C, 76.99;
H, 5.73; N, 5.30.
4.3.4. 1-(2,5-Dihydroxy-4-methoxybenzyl)isoquinoline
(11). Oil; yield 30%; H NMR (CDCl3) d 3.81 (s, 3H),
1
4.48 (s, 2H), 6.59 (s, 1H), 6.77 (s, 1H), 7.55 (d, 1H, JZ
6.5 Hz), 7.20–7.60 (m, 2H), 7.82 (d, 1H, JZ6.7 Hz), 8.34
(d, 1H, JZ6.1 Hz), 8.40 (d, 1H, JZ9.1 Hz); 13C NMR
(CDCl3) d 36.1, 56.2, 101.4, 122.8, 122.9, 125.9, 126.5,
126.9, 128.6, 131.6, 140.9, 144.2, 147.6, 153.6, 156.7; MS
m/z (%) 281 (100) [M]C, 280 (72), 167 (79); HRMS
(FAB) m/z calcd for C17H15NO3 (M)C281.1052; found
281.1059.
4.2.6. 1-(3-Hydroxy-4-methoxybenzyl)isoquinoline
N-oxide (5). An amount of 0.75 g (2.8 mmol) of 1-(3-
hydroxy-4-methoxybenzyl)isoquinoline13 was reacted as
for the preparation of 1. Brown solid; mpZ195–196 8C
(AcOEt); yield 73%; 1H NMR (CDCl3): d 3.79 (s, 3H,
–OCH3), 4.71 (s, 2H, –CH2–), 5.65 (s, 1H, OH), 6.71 (d, 1H,
4.3.5. 1-(2,3-Dihydroxy-4-methoxybenzyl)isoquinoline
(12). Oil; yield 15%; H NMR (CDCl3) d 3.77 (s, 3H),
1
4.53 (s, 2H), 6.36 (d, 1H, JZ8.5 Hz), 6.91 (d, 1H, JZ
8.5 Hz), 7.53 (d, 1H, JZ5.7 Hz), 7.62–7.69 (m, 2H), 7.79
(d, 1H, JZ7.3 Hz), 8.33–8.40 (m, 2H); 13C NMR (CDCl3) d
36.1, 56.3, 108.2, 122.8, 125.8, 126.5, 126.9, 127.2, 128.5,
131.6, 136.6, 138.5, 141.0, 144.0, 148.1, 157.5; MS m/z (%)
281 (100) [M]C, 168 (72), 167 (79); HRMS (FAB) m/z
calcd for C17H15NO3 (M)C: 281.1052; found 281.1057.
0
0
0
JZ7.9 Hz, H5 ), 6.80–6.86 (m, 2H, H2 , H6 ), 7.50–7.65 (m,
3H, H4, H6, H7), 7.76 (d, 1H, JZ8.2 Hz), 7.99 (d, 1H, JZ
8.5 Hz, H8), 8.22 (d, 1H, JZ7.3 Hz, H3); 13C NMR
(CDCl3): d 30.6, 55.4, 111.4, 115.0, 119.4, 120.3, 122.9,
124.2, 124.4, 127.2, 128.3, 129.1, 129.4, 129.8, 135.4,
146.0, 148.1; MS (EI, relative %) 281 (30) [M]C, 280 (60),
264 (100). Anal. Calcd for C17H15NO2 (281.31): C, 76.96;
H, 5.70; N, 5.28. Found: C, 76.99; H, 5.72; N, 5.29.
4.4. Theoretical calculations
4.2.7. 1-(2-Hydroxybenzyl)isoquinoline N-oxide (17).29
In order to ensure reliable results, density functional theory
(DFT) calculations were carried out by using the software
Gaussian 9822a on an SGI Origin 2000 supercomputer. We
used Becke’s three-parameter exchange functional in
combination with the LYP correlation functional
(B3LYP).22b The hybrid functional (HF/DFT) B3LYP was
previously shown to provide electronic spin densities
similar to those obtained from high-level CAS computations
with the same basis sets.22c We used the 6-31g(d,p) basis
set,22d which is a split-valence set and includes a series of
d-polarization functions on heavy atoms and p-polarization
4.3. General procedure for irradiation of samples
A 10K3 M solution of the corresponding N-oxide in CH2Cl2
and 0.1 M TFA was bubbled with argon and irradiated
through Pyrex at room temperature under an Ar atmosphere,
using a medium-pressure mercury lamp (150 W) for 10 min.
The solutions were then washed with aqueous NaHCO3 and
H2O, and dried over MgSO4. The solvent was evaporated
under reduced pressure and the resulting material separated