N. Briet et al. / Tetrahedron 58 (2002) 5761±5766
5765
The following compounds were prepared in a similar
manner.
8.60 (1H, s, NCHC), 8.00 (1H, d, J8.0 Hz, CFCHCHCH),
7.44±7.41 (1H, m, CFCH), 7.18 (1H, dd, J8.0, 7.0 Hz,
CFCHCH), 4.70 (1H, t, J4.0 Hz, CH2CH), 3.82 (2H, d,
J4.0 Hz, CH2CH) and 3.42 (6H, s, 2£OCH3). Rt
2.84 min; mass spectrum m/z 273 (M11, 100%).
2,3-Di¯uorobenzylidene)(2,2-dimethoxyethyl)amine (11 g,
68 mmol) was reacted with concentrated sulfuric acid to
yield the title compound as a orange solid (2.80 g, 25%);
4.2.12. 7,8-Dichloroisoquinoline (22b). From 2,3-dichloro-
benzaldehyde (30 g, 0.17 mol) and aminoacetaldehyde
dimethyl acetal (18 g, 0.20 mol), (2,3-dichlorobenzyl-
idene)(2,2-dimethoxyethyl)amine was yielded as a pale
orange-brown oil (45 g, quantitative); d 1H (300 MHz,
CDCl3) 8.74 (1H, s, NCHC), 7.96 (1H, dd, J7.5, 8.0 Hz,
CCH), 7.54 (1H, dd, J8.5, 7.5 Hz CFCH), 7.24 (1H, t,
J7.5 Hz, CFCHCH), 4.72 (1H, t, J4.0 Hz, CH2CH),
3.84 (2H, d, J4.0 Hz, CH2CH) and 3.44 (6H, s, 2£
OCH3). (2,3-Dichlorobenzylidene)(2,2-dimethoxyethyl)-
amine (45 g, 0.17 mol) was reacted with concentrated
sulfuric acid, to give the title compound as a brown solid
1
TLC Rf 0.45 (50% ethylacetate/hexane); d H (300 MHz,
CDCl3) 9.58 (1H, s, NCHC), 8.62 (1H, d, J7.5 Hz,
NCHCH), 7.52±7.70 (3H, m, NCHCH, CHCHCF); Rt
3.23 min; mass spectrum m/z 166 (M11, 100%).
4.2.16. 6,7-Dichloroisoquinoline 2-oxide (23a). 3-Chloro-
peroxybenzoic acid (57±86%, 0.716 g) was added to a solu-
tion of 6,7-dichloroisoquinoline (0.343 g, 1.73 mmol) in
dichloromethane (10 mL) at rt, and the mixture stirred for
2 h. The mixture was diluted with dichloromethane (50 mL)
and methanol (5 mL), and washed with sodium hydroxide
solution (2 M, 60 mL). The aqueous phase was extracted
with dichloromethane (2£20 mL), and the combined
organic phases dried (MgSO4) and concentrated. The resi-
due was chromatographed (eluent, 5±10% methanol/ethyl-
acetate) to give the title compound as a white solid (0.323 g,
87%); TLC Rf 0.26 (5% methanol/ethylacetate); d 1H
(300 MHz, CDCl3) 8.76 (1H, s, NCHC), 8.14 (1H, d, J
7.5 Hz, NCHCH), 7.92 (1H, s, CHCCl), 7.83 (1H, s,
CHCCl), 7.58 (1H, d, J7.5 Hz, NCHCH); Rt2.87 min;
mass spectrum m/z 166 (M11, 80%).
1
(12.5 g, 49%); TLC Rf 0.6 (ethylacetate). d H (300 MHz,
CDCl3) 9.70 (1H, s, NCHC), 8.65 (1H, d, J6.0 Hz,
NCHCH), 7.72 (2H, s, CHCHCCl), 7.66 (1H, d, J
6.0 Hz, NCHCH).
4.2.13. 8-Fluoroisoquinoline (22c). From 2-¯uorobenz-
aldehyde (20.8 g, 0.17 mol) and aminoacetaldehyde
dimethyl acetal (17.6 g, 0.19 mol), (2-¯uorobenzyl-
idene)(2,2-dimethoxyethyl)amine was yielded as a pale
orange-brown oil (35 g, quantitative); d 1H (300 MHz,
CDCl3) 8.60 (1H, s, NCHC), 8.00 (1H, dd, J8.0, 7.5 Hz,
CCH), 7.41±7.38 (1H, m, CFCH), 7.18 (1H, t, J8.0 Hz,
CCHCH), 7.08 (1H, t, J8.0 Hz, CFCHCH), 4.70 (1H, t,
J4.5 Hz, CH2CH), 3.82 (1H, t, J4.5 Hz, CH2CH)
and 3.42 (6H, s, 2£OCH3). (2-Fluorobenzylidene)(2,2-di-
methoxyethyl)amine (35 g, 0.17 mol) was reacted with
concentrated sulfuric acid to yield the title compound as a
pale yellow solid (0.7 g, 3%); TLC Rf 0.45 (50% ethyl-
acetate/hexane); d 1H (300 MHz, CDCl3) 9.60 (1H, s,
NCHC), 8.62 (1H, d, J7.0 Hz, NCHCH), 7.68±7.60 (2H,
m, CHCCH), 7.26±7.20 (1H, m, CFCH).
4.2.17. 7,8-Dichloroisoquinoline 2-oxide (23b). From 7,8-
dichloroisoquinoline (2.00 g, 0.20 mol) and 3-chloroperoxy-
benzoic acid (57±86%, 4.18 g), without chromatography,
to give the title compound as a white solid (1.81 g, 84%);
1
TLC Rf 0.19 (5% methanol/ethylacetate); d H (300 MHz,
CDCl3) 9.14 (1H, s, NCHC), 8.18 (1H, d, J9.0 Hz,
NCHCH), 7.71±7.58 (3H, m, NCHCH, CHCHCCl); Rt
3.36 min; mass spectrum m/z 214 (M1, 100%), 197 (30).
4.2.14. 8-Bromoisoquinoline (22d). From 2-bromobenz-
aldehyde (10 g, 54 mmol) and aminoacetaldehyde dimethyl
acetal (5.89 mL, 54 mmol), (2-bromobenzylidene)(2,2-di-
methoxyethyl)amine was yielded as a pale orange-brown
4.2.18. 8-Fluoroisoquinoline 2-oxide (23c). From 8-¯uoro-
isoquinoline (0.69 g, 4.63 mmol) and 3-chloroperoxy-
benzoic acid (57±86%, 1.62 g), without chromatography,
to give the title compound as a pale beige solid (0.73 g,
95%); TLC Rf 0.05 (ethylacetate). d 1H (300 MHz,
CDCl3) 8.96 (1H, s, NCHC), 8.16 (1H, d, J7.5 Hz,
NCHCH), 7.70 (1H, d, J7.5 Hz, NCHCH), 7.64±7.50
(2H, m, CFCHCHCH), 7.34±7.26 (1H, m, CFCHCH).
1
oil (15 g, quantitative); d H (300 MHz, CDCl3) 8.60 (1H,
s, NCHC), 8.00 (1H, d, J9.0 Hz, CCH), 7.52 (1H, d,
J8.0 Hz, CBrCH), 7.38±7.12 (2H, m, CHCHCHCH),
4.70 (1H, t, J4.5 Hz, CH2CH), 3.82 (2H, d, J4.5 Hz,
CH2CH) and 3.42 (6H, s, 2£OCH3). Rt2.56 min;
mass spectrum m/z 273 (M11, 100%). (2-Bromobenzyl-
idene)(2,2-dimethoxyethyl)amine (15 g, 54 mmol) was
reacted with concentrated sulfuric acid and puri®ed by
¯ash chromatography (eluent 40% hexane/ethylacetate) to
give the title compound as a beige yellow solid (0.19 g,
1.8%); TLC Rf 0.45 (50% ethylacetate/hexane), d 1H
(300 MHz, CDCl3) 9.68 (1H, s, NCHC), 8.64 (1H, d,
J7.0 Hz, NCHCH), 7.88 (1H, d, J8.5 Hz, CBrCH),
7.80 (1H, d, J8.5 Hz, CBrCHCHCH), 7.62 (1H, d, J
7.0 Hz, NCHCH), 7.52 (1H, t, J8.54 Hz, CBrCHCH);
Rt2.92 min; mass spectrum m/z 208 (M1, 100%), 129 (15).
4.2.19. 8-Bromoisoquinoline 2-oxide (23d). From
8-bromoisoquinoline (0.19 g, 0.89 mmol) and 3-chloro-
peroxybenzoic acid (28%, 0.26 mL), without chroma-
tography, to give the title compound as a pale beige solid
(0.16 g, 84%); TLC Rf 0.25 (10% methanol/ethylacetate). d
1H (300 MHz, CDCl3) 9.16 (1H, s, NCHC), 8.18 (1H, d,
J9.0 Hz, NCHCH), 7.88 (1H, d, J8.0 Hz, CBrCH),
7.74 (1H, d, J8.0 Hz, CBrCHCHCH), 7.64 (1H, d, J
9.0 Hz, NCHCH), 7.44 (1H, t, J8.0 Hz, CBrCHCHCH);
Rt2.93 min; mass spectrum m/z 225 (M11, 100%).
4.2.15. 7,8-Di¯uoroisoquinoline (22e). From 2, 3-di¯uoro-
benzaldehyde (9.7 g, 68 mmol) and aminoacetaldehyde
dimethyl acetal (7.17 g, 68 mmol), to give (2,3-d¯uoro-
benzylidene)(2,2-dimethoxyethyl)amine as a pale orange-
brown oil (11 g, quantitative); d 1H (300 MHz, CDCl3)
4.2.20. 7,8-Di¯uoroisoquinoline 2-oxide (23e). From 7,8-
di¯uoroisoquinoline (0.80 g, 4.85 mmol) and 3-chloro-
peroxybenzoic acid (57±86%, 1.00 g), without chroma-
tography, to give the title compound as a white solid