1
C-6), 163.5 (d, JCF 237.4, C-2); δF(235 MHz) Ϫ67.9 (s); m/z
line 4b (0.52 g, 85%, 56% conversion) as white needles; mp 75–
76 ЊC (vacuum sublimation oil bath temp. 50 ЊC/<1 mmHg);
Rf 0.69 (Found: C, 47.5; H, 2.1; N, 6.2. C9H5BrFN requires: C,
(EIϩ) 97 (Mϩ, 100%), 70 (68), 69 (12), 57 (18), 50 (29), 39 (22);
as compared to the literature data;10 and 2,6-difluoropyridine
(3% by GC); m/z (EIϩ) 115 (Mϩ, 100%), 88 (22), 70 (54), 57 (13).
47.8; H, 2.2; N, 6.2%); δH(400 MHz) 7.55 (1 H, dd, JH5,H6
=
JH6,H7 8.0, H-6), 7.74 (1 H, ddd, JH7,H8 8.4, JH6,H7 7.2, JH5,H7 1.2,
H-7), 7.76 (1 H, d, JH5,H6 8.0, H-5), 7.91 (1 H, dd, JH7,H8 8.4,
JH6,H8 0.8, H-8), 8.42 (1 H, d, JH4,F 8.4, H-4); δC(100 MHz) 104.0
(d, 2JCF 43.2, C-3), 126.6 (s, C-6), 127.0 (d, 4JCF 2.7, C-8), 128.0
4-Ethylpyridine 1b. 4-Ethylpyridine 1b (12.8 g, 120 mmol)
and iodine (30.5 g, 120 mmol) in CFCl2CF2Cl (150 ml) and
fluorine (165 mmol) gave a yellow oil (9.54 g) which contained
1b, 2-fluoro-4-ethylpyridine 2b and other minor products by
GC-MS The oil was redissolved in dichloromethane and
washed with 2 M HCl solution, dried (MgSO4) and evaporated
to give 2-fluoro-4-ethylpyridine 2b (6.3 g, 54%, 78% conversion)
as a clear oil in >95% purity by GC; δH(200 MHz) 1.26 (3 H, t,
3JHH 7.6, CH3), 2.69 (2 H, q, 3JHH 7.6, CH2), 6.75 (1 H, s, H-3),
7.02 (1 H, dm, 3JH5,H6 5.1, H-5), 8.09 (1 H, d, 3JH5,H6 5.1, H-6);
δC(50 MHz) 14.1 (s, CH3), 28.2 (d, 4JCF 2.7, CH2), 108.5 (d, 2JCF
5
4
5
(d, JCF 1.9, C-5) 128.0 (d, JCF 2.2, C-4a), 130.9 (d, JCF 1.1,
3
3
C-7), 143.5 (d, JCF 3.7, C-4), 144.2 (d, JCF 15.1, C-8a), 157.3
(d, 1JCF 238.1, C-2); δF(235 MHz) Ϫ60.8 (s); m/z (EIϩ) 225 (Mϩ,
100%), 227 (Mϩ, 74), 146 (56), 126 (23), 101 (18), 75 (14).
4-Chloroquinoline 3c. 4-Chloroquinoline 3c (1.0 g, 6 mmol),
iodine (1.55 g, 6 mmol) and triethylamine (0.60 g, 6 mmol)
in CFCl2CF2Cl (30 ml) and fluorine (7 mmol) gave a brown
oil (1.01 g). Column chromatography gave 2-fluoro-4-chloro-
quinoline 4c (0.76 g, 90%, 76% conversion) as white needles; mp
60–61 ЊC (vacuum sublimation oil bath temp. 50 ЊC/<1 mmHg);
Rf 0.78 (Found: C, 59.7; H, 2.9; N, 7.6. C9H5ClFN requires: C,
59.5; H, 2.75; N, 7.7%); δH(400 MHz) 7.20 (1 H, d, JH3,F 2.4,
H-3), 7.62 (1 H, ddd, JH5,H6 = JH6,H7 7.4, JH6,H8 1.2, H-6), 7.78
(1 H, ddd, JH6,H7 = JH7,H8 7.8, JH5,H7 1.2, H-7), 7.96 (1 H, d,
JH7,H8 8.4, H-8), 8.19 (1 H, d, JH5,H6 8.4, H-5); δC(100 MHz)
110.2 (d, 2JCF 45.8, C-3), 124.2 (d, 5JCF 0.8, C-5), 125.1 (d, 4JCF
2.6, C-4a), 127.0 (d, 6JCF 2.7, C-6), 128.5 (d, 4JCF 1.5, C-8), 131.6
(s, C-7), 145.9 (d, 3JCF 18, C-8a), 146.6 (d, 3JCF 12.5, C-4), 160.2
(d, 1JCF 242.3, C-2); δF(235 MHz) Ϫ61.5 (s); m/z (EIϩ) 183 (Mϩ,
26%), 181 (Mϩ, 100), 146 (35), 126 (15), 75 (12), 50 (11).
4
3
36.5, C-3), 121.3 (d, JCF 3.9, C-5), 147.3 (d, JCF 15.2, C-6),
159.3 (d, 3JCF 7.8, C-4), 164.2 (d, 1JCF 236.3, C-2); δF(235 MHz)
Ϫ69.9 (s); m/z (EIϩ) 125 (Mϩ, 100%), 110 (47), 97 (15), 83 (13);
as compared to the literature data.19
2-Chloropyridine. 2-Chloropyridine 1c (3.0 g, 26 mmol),
iodine (6.7 g, 26 mmol) and triethylamine (2.7 g, 26 mmol) in
CFCl2CF2Cl (150 ml) and fluorine (35 mmol) gave a brown oil
(2.5 g) which contained 2a (10%) and 2-chloro-6-fluoropyridine
2c (50%) by GC-MS analysis. Purification by column chrom-
atography gave 2-chloro-6-fluoropyridine 2c (1.25 g, 70%, 61%
conversion) as white crystals; mp 35–36 ЊC (lit.,26 34–36 ЊC); Rf
0.77; δH(200 MHz) 6.86 (1 H, ddd, JH4,H5 8.1, JH5,F 2.7, JH3,H5
0.6, H-5), 7.21 (1 H, ddd, JH3,H4 7.7, JH3,F 1.6, JH3,H5 0.6, H-3),
7.75 (1 H, pseudo q, JH3,H4 = JH4,H5 = JH4,F = 7.9, H-4); δC(50
MHz) 109.8 (d, 2JCF 34.8, C-5), 123.6 (s, C-3), 145.0 (d, 3JCF 7.5,
C-4), 150.8 (d, 3JCF 13.5, C-2), 164.2 (d, 1JCF 244.2, C-6); δF(235
MHz) Ϫ66.3 (s); m/z (EIϩ) 131 (Mϩ, 100%), 133 (Mϩ, 33), 96
(64), 76 (20), 51 (14); as compared to the literature data.16,19
4-Methylquinoline 3d.28 4-Methylquinoline 3d (5.0 g, 35
mmol) and iodine (9.0 g, 35 mmol) in CFCl2CF2Cl (30 ml) and
fluorine (40 mmol) gave a brown oil (3.7 g). Column chrom-
atography gave 2-fluoro-4-methylquinoline 4d (1.6 g, 49%, 58%
conversion) as an oil which was homogeneous by GC; δH(200
MHz) 2.64 (3 H, s, CH3), 6.83 (1 H, s, H-3), 7.51 (1 H, m, H-6),
7.66 (1 H, m, H-7), 7.87 (2 H, m, H-5 and H-8); δC(50 MHz)
18.9 (d, 4JCF 2.6, CH3), 109.9 (d, 2JCF 41.6, C-3), 123.8 (s, C-6),
125.8 (d, 4JCF 2.3, C-8), 126.8 (d, 4JCF 1.8, C-4a), 128.5 (d, 5JCF
1.5, C-5), 130.3 (s, C-7), 145.5 (d, 3JCF 17.5, C-8a), 151.0 (d, 3JCF
2-Bromopyridine 1d. 2-Bromopyridine 1d (4.1 g, 26 mmol),
iodine (6.7 g, 26 mmol), triethylamine (2.7 g, 26 mmol) in
CFCl2CF2Cl (150 ml) and fluorine (35 mmol) gave a brown oil
which contained triethylamine (23%), 2a (25%) and 2-bromo-6-
fluoropyridine 2d (51%) by GC-MS analysis. Purification by
column chromatography gave 2-bromo-6-fluoropyridine 2d
(2.7 g, 59%, 100% conversion) as white crystals; mp 30–32 ЊC;
Rf 0.78; δH(200 MHz) 6.90 (1 H, ddd, JH4,H5 8.0, JH4,F 2.7, JH3,H5
1
10.2, C-4), 161.0 (d, JCF 241.1, C-2); δF(235 MHz) Ϫ59.3 (s);
m/z (EIϩ) 161 (Mϩ, 67%), 143 (100), 133 (11), 115 (52), 89 (29).
6-Chloroquinoline 3e. 6-Chloroquinoline 3e (1.0 g, 6.1 mmol),
iodine (1.55 g, 6.1 mmol) and triethylamine (0.62 g, 6.2 mmol)
in CFCl2CF2Cl (30 ml) and fluorine (7 mmol) gave a brown
solid (0.93 g). Column chromatography gave 2-fluoro-6-
chloroquinoline 4e (0.73 g, 82%, 81% conversion) as a white
solid; mp 60–61 ЊC (vacuum sublimation oil bath temp. 60 ЊC/
<1 mmHg); Rf 0.78 (Found: C, 59.6; H, 2.9; N, 7.5. C9H5ClFN
requires: C, 59.5; H, 2.75; N, 7.7%); δH(400 MHz) 7.12 (1 H, dd,
JH3,H4 8.8, JH3,F 2.8, H-3), 7.67 (1 H, dd, JH7,H8 9.2, JH5,H7 2.4,
H-7), 7.82 (1 H, d, JH5,H7 2.4, H-5), 7.87 (1 H, d, JH7,H8 9.0, H-8),
8.16 (1 H, dd, JH3,H4 = JH4,F 8.8, H-4); δC(100 MHz) 111.1 (d,
2JCF 42.3, C-3), 126.3 (s, C-5), 127.3 (s, C-4a), 129.6 (s, C-8),
0.5, H-5), 7.37 (1 H, m, H-3), 7.66 (1 H, pseudo q, JH3,H4
=
JH4,H5 = JH4,F = 7.9, H-4); δC(50 MHz) 110.2 (d, 2JCF 34.6, C-5),
4
3
127.5 (d, JCF 4.8, C-3), 140.6 (d, JCF 13.5, C-Br), 144.8 (d,
3JCF 7.5, C-4), 164.1 (d, JCF 245.1, C-F); δF(235 MHz) Ϫ65.5
1
(s); m/z (CIϩ, NH3) 176 (Mϩ ϩ 1, 26%), 178 (Mϩ ϩ 1, 22), 98
(100).
Quinoline 3a. Quinoline 3a (18.0 g, 139 mmol) and iodine
(35.3 g, 139 mmol) in CFCl2CF2Cl (250 ml) and fluorine
(165 mmol) gave an orange oil (12.4 g). Distillation afforded
2-fluoroquinoline 4a (8.3 g, 54%, 77% conversion) as a pale
yellow oil; bp30 134–136 ЊC (lit.,11 bp30 133 ЊC); δH(400 MHz)
7.05 (1 H, dd, JH3,H4 8.8, JH3,F 2.8, H-3), 7.51 (1 H, ddd, JH5,H6
8.0, JH6,H7 6.8, JH6,H8 0.8, H-6), 7.71 (1 H, ddd, JH7,H8 8.0, JH6,H7
7.6, JH5,H7 1.2, H-7), 7.81 (1 H, d, JH5,H6 8.0, H-5), 7.94 (1 H, d,
JH7,H8 8.4, H-8), 8.20 (1 H, dd, JH3,H4 = JH4,F 8.4, H-4); δC(100
3
131.4 (s, C-7), 131.9 (s, C-6), 141.0 (d, JCF 9.9, C-4), 144.1 (d,
3JCF 16.8, C-8a), 161.2 (d, 1JCF 243.8, C-2); δF(235 MHz) Ϫ61.5
(s); m/z (EIϩ) 181 (Mϩ, 100%), 183 (Mϩ, 32), 146 (34), 126 (11).
4,7-Dichloroquinoline 3f. 4,7-Dichloroquinoline 3f (1.0 g, 5
mmol), iodine (1.28 g, 5 mmol) and triethylamine (0.51 g, 5.1
mmol) in CFCl2CF2Cl (30 ml) gave a brown oil (1.06 g). Col-
umn chromatography gave 2-fluoro-4,7-dichloroquinoline 4f
(0.66 g, 88%, 69% conversion) as white crystals; mp 105–106 ЊC
(vacuum sublimation oil bath temp. 60 ЊC/<1 mmHg); Rf 0.72
(Found: C, 49.7; H, 1.7; N, 6.3. C9H4Cl2FN requires: C, 50.0; H,
1.85; N, 6.5%); δH(400 MHz) 7.20 (1 H, d, JH3,F 2.4, H-3), 7.58
(1 H, dd, JH5,H6 9.0, JH6,H8 2.2, H-6), 7.95 (1 H, d, JH6,H8 2.0,
H-8), 8.13 (1 H, d, JH5,H6 9.2, H-5); δC(100 MHz) 110.38 (d, 2JCF
45.8, C-3), 123.6 (d, 4JCF 2.3, C-4a), 125.5 (s, C-6), 127.6 (d, 5JCF
2
4
MHz) 110.0 (d, JCF 42.1, C-3), 126.1 (d, JCF 2.6, C-8), 126.8
(d, 4JCF 1.9, C-4a), 127.5 (s, C-6), 128.0 (d, 5JCF 1.2, C-5), 130.6
5
3
3
(d, JCF 0.8, C-7), 141.9 (d, JCF 9.9, C-4), 145.7 (d, JCF 16.7,
1
C-8a), 161.1 (d, JCF 240.5, C-2); δF(250 MHz) Ϫ63.2 (s); m/z
(EIϩ) 147 (Mϩ, 100%); as compared to the literature data.11,27
3-Bromoquinoline 3b. 3-Bromoquinoline 3b (1.0 g, 4.8 mmol),
iodine (1.22 g, 4.8 mmol) and triethylamine (0.48 g, 4.8 mmol)
in CFCl2CF2Cl (30 ml) and fluorine (5 mmol) gave a brown oil
(0.95 g). Column chromatography gave 2-fluoro-3-bromoquino-
J. Chem. Soc., Perkin Trans. 1, 1999, 803–810
807