R.D. Chambers et al. / Journal of Fluorine Chemistry 125 (2004) 661–671
669
4.0, H-5), 7.89 (1 H, dd, 3JHH 8.5, 4JHH 1.5, H-4); dF –131.8
(s, F-8); dC 14.6 (d, 3JCF 4.3, 7-Me), 25.5 (s, 2-Me), 122.0 (s,
C-3), 122.1 (d, JCF 5.3, C-5), 123.3 (d, JCF 15.8, C-7),
equiv) gave a yellow solid (1.6 g, conv. 66%) which con-
tained 2-chloro-5-fluoro-6-methoxyquinoline-3-carbalde-
hyde 16a (73%) and 2-chloro-5,5-difluoro-6-oxo-5-
hydroquinoline-3-carbaldehyde 16b (27%). Purification by
column chromatography on silica gel using hexane: diethyl
ether (7:3) then dichloromethane as elutant, gave 2-chloro-
5-fluoro-6-methoxyquinoline-3-carbaldehyde 16a as a yel-
low solid; mp 146–1478C; (Found: C, 54.87; H, 2.91; N,
5.80. C11H7ClFNO2 requires C, 55.14; H, 2.94; N, 5.85%);
dH 4.06 (3 H, s, OMe), 7.66 (1 H, t, 3JHH ¼ 4JHF 9.0, H-7),
7.83 (1 H, d, 3JHH 9.9, H-8), 8.91 (1 H, s, H-4), 10.52 (1 H, s,
4
2
126.2 (d, 3JCF 2.4, C-4a), 128.4 (d, 3JCF 4.8, C-6), 135.6 (d,
2
1
4JCF 3.4, C-4), 137.9 (d, JCF 11.9, C-8a), 155.1 (d, JCF
251.0, C-8), 159.2 (d, JCF 6.0, C-2); m/z (EIþ) 175 (Mþ,
4
100%), 174 (79); Mþ, 175.079991. C11H10FN requires M,
175.079728; (Found: C, 74.91; H, 5.59; N, 7.87. C11H10FN
requires C, 75.41; H, 5.75; N, 7.99%); and, 5,8-difluoro-2,7-
dimethylquinoline 11b as a white solid; dH 2.46 (3 H, d, 4JHF
2.4, 7-Me), 2.78 (3 H, s, 2-Me), 6.95 (1 H, dd, 3JHF 10.0, 4JHF
5.2, H-6), 7.31 (1 H, d, 3JHH 8.8, H-3), 8.21 (1 H, d, 3JHH 8.8,
H-4); dF À129.2 (1 F, dd, 5JFF 21.8, 3JHF 9.4, F-5), À135.9 (1
4
4
CHO); dF À141.8 (d, JHF 8.6, F-5); dC 57.5 (d, JCF 1.0,
OMe), 118.3 (d, 2JCF 13.7, C-4a), 122.7 (d, 3JCF 2.8, C-7),
124.6 (d, 4JCF 4.5, C-8), 126.4 (d, 3JCF 2.3, C-8a), 133.2 (d,
4JCF 4.5, C-4), 143.6 (s, C-2), 144.4 (d, 2JCF 8.7, C-6), 146.7
5
3
F, d, JFF 21.1, F-8); dC 14.9 (d, JCF 3.1, 7-Me), 25.6 (s,
2-Me), 111.5 (dd, 2JCF 21.4, 3JCF 4.6, C-6), 116.3 (dd, 2JCF
3
4
1
18.6, JCF 2.3, C-4a), 122.1 (d, JCF 2.2, C-3), 123.1 (dd,
(d, JCF 257.3, C-5), 148.5 (s, CHO), 188.6 þ(m, C-3); m/z
2JCF 18.0, JCF 8.4, C-7), 129.3 (t, JCF ¼ 4JCF 2.7, C-4),
(EIþ) 241 (Mþ [37Cl], 75%), 240 (66), 239 (M [35Cl], 100),
241 (75), 238 (74), 224 (78), 196 (82), 175 (86), 168 (70),
132 (86); and, 2-chloro-5,5-difluoro-6-oxo-5-hydroquino-
line-3-carbaldehyde 16b as a yellow solid; mp 122–
123 8C; (Found: C, 49.13; H, 1.59; N, 5.71. C10H4ClF2NO
requires C, 49.31; H, 1.66; N, 15.60%); dH 6.64 (1 H, dt,
3JHH 10.0, 4JHF 2.5, H-7), 7.64 (1 H, d, 3JHH 10.5, H-8), 8.58
(1 H, s, H-4), 10.45 (1 H, s, CHO); dF –102.4 (2 F, s, F-5); dC
104.1 (t, 1JCF 248.1, C-5), 128.5 (s, C-2), 129.1 (t, 2JCF 25.1,
C-4a), 130.0 (t, 3JCF 2.8, C-7), 136.7 (t, 3JCF 2.3, C-4), 143.9
(s, C-8), 153.3 (t, 3JCF 5.9, C-8a), 156.1þ(s, CHO), þ184.9 (t,
2JCF 24.3, C-6), 187.2 (m, C-3); m/z (EI ) 245 (M [37Cl],
74%), 243 (Mþ [35Cl], 100), 217 (60), 216 (67), 215 (80),
214 (97), 186 (86), 179 (51), 152 (68), 151 (88), 125 (65),
100 (52), 99 (67), 75 (81).
3
3
137.9 (dd, 2JCF 13.7, 3JCF 3.8, C-8a), 151.4 (dd, 1JCF 246.3,
4JCF 3.8, C-5), 152.8 (dd, JCF 249.0, 4JCF 3.8, C-8), 160.4
1
(s, C-2); m/z (EIþ) 193 (Mþ, 100%); Mþ, 193.070315.
C11H9F2N requires M, 193.070306.
3.2.8. Fluorination of 6-methoxyquinoline 13
6-Methoxyquinoline 13 (2.50 g, 16 mmol), sulfuric acid
(150 ml) and fluorine (52 mmol, 3.25 equiv.) gave an orange
oil (3.43 g, conv. 71%) that contained 5-fluoro-6-methox-
yquinoline 14a (74%) and 5,5-difluoro-5-hydroquinoline-6-
one 14b (26%). Purification by column chromatography on
silica gel using diethyl ether as elutant, gave 5-fluoro-6-
methoxyquinoline 14a (1.1 g) as a white solid; mp 44–
46 8C; (Found: C, 67.76; H, 4.56; N, 8.03. C10H8FNO
requires C, 67.79; H, 4.55; N, 7.91%); dH 7.36 (1 H, dd,
3JHH 8.4, 5JHF 4.0, H-8), 7.48 (1 H, t, 3JHH ¼ 4JHF 9.2, H-7),
7.85 (1 H, dm, 3JHH 9.2, H-3), 8.31 (1 H, dm, 3JHF 8.4, H-4),
8.78 (1 H, dd, 4JHH 4.0, 3JHH 1.6, H-2); dF –147.5 (s, F-5); dC
15 (10.4 g, 47 mmol), sulphuric acid (150 ml) and fluor-
ine (707 mmol, 15 equiv.) gave a yellow solid (10.23 g,
100% conv.), which consisted of 16b (10.23 g, 89%) as the
sole product and no further purification was necessary;
spectral and physical data as above.
3
57.4 (d, 4JCF 1.1, MeO), 118.5 (d, JCF 2.7, C-7), 119.6 (d,
2JCF 13.7, C-4a), 121.2 (d, 3JCF 3.1, C-3), 125.4 (d, 4JCF 4.5,
4
2
C-8), 128.0 (d, JCF 5.3, C-4), 143.1 (d, JCF 14.4, C-6),
143.2 (d, 3JCF 7.2, C-8a), 145.1 (d, 1JCF 250.0, C-5), 149.0
(s, C-2); m/z (EIþ) 177 (Mþ, 100%), 134 (76); and, 5,5-
difluoro-5-hydroquinolin-6-one 14b (0.44 g) as a yellow
solid; mp 105–107 8C; (Found: C, 59.68; H, 2.77; N,
7.82. C9H5FNO requires C, 59.68; H, 2.78; N, 7.73%);
dH 6.46 (1 H, dt, JHH 10.4, JHF 4.0, H-7), 7.44 (1 H,
dd, 3JHH 7.6, 4JHH 9.2, H-3), 7.64 (1 H, d, 3JHH 10.4, H-8),
8.10 (1 H, dm, 4JHF 8.1, H-4), 8.75 (1H, dq, 3JHH 4.8, 4JHH
1.2, H-2); dF –102.4 (2 F, s, F-5); dC 104.9 (t, 1JCF 245.0, C-
5), 124.4 (s, C-3), 126.8 (t, 3JCF 2.7, C-7), 129.7 (t, 2JCF 24.3,
C-4a), 134.7 (t, 3JCF 2.7, C-4), 146.9 (s, C-8), 149.3 (t, 3JCF
6.1, C-8a), 152.8 (t, 5JCF 1.9, C-2), 186.2 (t, 2JCF 24.2, C-6);
m/z (EIþ) 181 (Mþ, 100%), 153 (82).
3.2.10. Fluorination of 6-methoxy-8-nitroquinoline 17
6-Methoxy-8-nitroquinoline 17 (0.5 g, 2.5 mmol), sulfu-
ric acid (15 ml), PP11 (85 ml) and fluorine (36 mmol,
14 equiv.) gave a yellow/orange solid (0.45 g, conv. 59%)
which contained 5-fluoro-6-methoxy-8-nitroquinoline 18 as
the only product. Purification by column chromatography on
silica gel using diethyl ether: hexane (9:1) as elutant, gave 5-
fluoro-6-methoxy-8-nitroquinoline 18 (0.28 g) as a yellow
solid; mp 154–155 8C; (Found: C, 53.8; H, 3.0; N, 12.4.
C10H7FNO3 requires C, 54.1; H, 3.2; N, 12.6%); dH 4.01 (3
H, d, 5JHF 0.8, OMe), 7.57 (1 H, dd, 3JHH 8.8, 3JHH 4.4, H-3),
8.01 (1 H, d, 4JHF 8.0, H-7), 8.44 (1 H, d, 3JHH 8.4, 4JHH 1.6,
3
4
3
4
H-4), 9.01 (1 H, dd, JHH 4.4, JHH 1.6, H-2); dF –136.5
4
3
(d, JHF 7.9, F-5); dC 57.8 (s, OMe), 114.4 (d, JCF 3.6,
2
4
C-7), 119.9 (d, JCF 14.2, C-4a), 122.8 (d, JCF 3.6, C-3),
3
3
3.2.9. Fluorination of 2-chloro-6-methoxyquinoline-3-
carbaldehyde 15
2-Chloro-6-methoxyquinoline-3-carbaldehyde 15 (1.5 g,
8 mmol), sulfuric acid (150 ml) and fluorine (48 mmol, 6
128.4 (d, JCF 5.1, C-4), 134.8 (d, JCF 2.8, C-8a), 142.1
2
1
(d, JCF 10.6, C-6), 143.6 (s, C-8), 147.2 (d, JCF 259.7,
C-5), 151.4 (s, C-2); m/z (EIþ) 222 (Mþ, 100%), 192 (84),
133 (52).