C.-C. Hu et al.
Journal of Fluorine Chemistry 242 (2021) 109695
%). 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J =5.7 Hz, 1 H), 6.91 (d, J
=2.5 Hz, 1 H), 6.69 (dd, J = 5.7, 2.6 Hz, 1 H), 5.38 (d, J =46.9 Hz, 2 H),
[M]+ Calculated for C6H4Cl2FN: 178.9699; Found: 178.9697.
3.80 (s, 3 H). 19F NMR (376 MHz, CDCl3) δ -221.89 (t, J =46.9 Hz). 13
C
4.4.8. 6-(Fluoromethyl)-4,4′-dimethyl-2,2′-bipyridine (2h)
NMR (101 MHz, CDCl3) δ 166.6, 158.2 (d, J =21.0 Hz), 150.4 (d, J
=2.3 Hz), 109.3, 106.2 (d, J =6.5 Hz), 84.2 (d, J =170.4 Hz), 55.2. IR
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2 h was obtained as a yellow solid (58.8 mg,
68 %). M.P. 46ꢀ 48 ◦C. 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J =5.0 Hz,
1 H), 8.19 (s, 1 H), 8.15 (s, 1 H), 7.29 (s, 1 H), 7.12 (d, J =5.1 Hz, 1 H),
5.53 (d, J =47.1 Hz, 2 H), 2.45 (s, 3 H), 2.42 (s, 3 H). 19F NMR
(376 MHz, CDCl3) δ -220.26 (t, J =47.2 Hz). 13C NMR (101 MHz, CDCl3)
δ 156.0, 155.8 (d, J =2.8 Hz), 155.7, 149.2, 149.0, 148.4, 124.9, 122.3,
121.53 (d, J =5.5 Hz), 121.46, 84.8 (d, J =169.3 Hz), 21.4, 21.3. IR
(thin film)
ν 3403, 2948, 2840, 1602, 1571, 1488, 1460, 1374, 1306,
836, 759 cmꢀ 1; MS (EI): m/z 141 [M]+; HRMS (EI) m/z: [M]+ Calculated
for C7H8FNO: 141.0584; Found: 141.0587.
4.4.3. 4-Benzyloxy-2-(fluoromethyl)pyridine (2c)
After purification by silica gel column chromatography (hexane/
EtOAc = 5:1), compound 2c was obtained as a yellow oil (68.6 mg, 79
%). 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J =5.7 Hz, 1 H), 7.50ꢀ 7.30
(m, 5 H), 7.06 (s, 1 H), 6.81 (d, J =3.3 Hz, 1 H), 5.44 (d, J =46.9 Hz,
2 H), 5.13 (s, 2 H). 19F NMR (376 MHz, CDCl3) δ -221.95 (t, J =46.8 Hz).
13C NMR (101 MHz, CDCl3) δ 165.8, 158.4 (d, J =21.2 Hz), 150.6 (d, J
=2.2 Hz), 135.6, 128.9, 128.5, 127.7, 110.0, 107.1 (d, J =6.5 Hz), 84.3
(thin film)
ν
2952, 1598, 1562, 1434, 1361, 1034, 830, 530 cmꢀ 1; MS
(EI): m/z 216.0 [M]+; HRMS (EI) m/z: [M]+ Calculated for C13H13FN2:
216.1057; Found: 216.1054.
4.4.9. 2-(Fluoromethyl)quinoline (2i)
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2i was obtained as a yellow oil (43.8 mg, 68
%). 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J =8.5 Hz, 1 H), 8.02 (d, J
=8.2 Hz, 1 H), 7.73 (d, J =8.2 Hz, 1 H), 7.66 (dd, J = 8.5, 6.9 Hz, 1 H),
7.51ꢀ 7.45 (m, 2 H), 5.61 (d, J =47.0 Hz, 2 H). 19F NMR (376 MHz,
CDCl3) δ -221.20 (t, J =47.0 Hz). 13C NMR (101 MHz, CDCl3) δ 156.7 (d,
J =21.7 Hz), 147.3 (d, J =1.8 Hz), 137.0, 130.0, 129.0, 127.7, 127.6,
(d, J =170.4 Hz), 70.0. IR (thin film)
ν 3030, 2852, 1598, 1569, 1483,
1310, 1177, 1026, 741, 697 cmꢀ 1; MS (EI): m/z 217 [M]+; HRMS (EI) m/
z: [M]+ Calculated for C13H12FNO: 217.0897; Found: 217.0900.
4.4.4. 4-Bromo-2-(fluoromethyl)pyridine (2d)
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2d was obtained as a yellow oil (37.2 mg, 49
%). 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J =5.3 Hz, 1 H), 7.64 (s, 1 H),
7.41 (dd, J = 5.3, 1.9 Hz, 1 H), 5.46 (d, J =46.7 Hz, 2 H). 19F NMR
(376 MHz, CDCl3) δ -223.06 (t, J =46.7 Hz). 13C NMR (101 MHz, CDCl3)
δ 158.0 (d, J =21.9 Hz), 149.9 (d, J =2.2 Hz), 134.1, 126.5, 123.9 (d, J
126.6, 118.1 (d, J =5.1 Hz), 85.0 (d, J =170.3 Hz). IR (thin film) ν 3056,
2952, 1601, 1507, 1429, 1376, 1038, 825, 753 cmꢀ 1; MS (EI): m/z 161.0
[M]+; HRMS (EI) m/z: [M]+ Calculated for C10H8FN: 161.0635; Found:
161.0632.
=6.6 Hz), 83.6 (d, J =171.6 Hz). IR (thin film)
ν
3056, 2922, 1574,
4.4.10. 2-(Fluoromethyl)-3-methoxyquinoline (2j)
1469, 1454, 1372, 1229, 1029, 825, 682 cmꢀ 1; MS (EI): m/z 188.9 [M]+;
HRMS (EI) m/z: [M]+ Calculated for C6H5BrFN: 188.9584; Found:
188.9585.
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2 j was obtained as a yellow oil (45.1 mg, 59
%). 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J =8.7 Hz, 1 H), 7.69 (d, J
=8.0 Hz, 1 H), 7.60ꢀ 7.41 (m, 2 H), 7.36 (s, 1 H), 5.68 (d, J =47.1 Hz,
2 H), 3.92 (s, 3 H). 19F NMR (376 MHz, CDCl3) δ -221.44 (t, J =47.1 Hz).
13C NMR (101 MHz, CDCl3) δ 151.6, 148.4 (d, J =14.7 Hz), 142.6,
129.4, 127.5, 127.1, 126.5, 112.4, 81.7 (d, J =169.3 Hz), 55.6. IR (thin
4.4.5. 2-(Fluoromethyl)-6-phenylpyridine (2e)
After purification by silica gel column chromatography (hexane/
EtOAc = 15:1), compound 2e was obtained as a yellow oil (33.7 mg, 45
%). 1H NMR (400 MHz, CDCl3) δ 8.03ꢀ 7.97 (m, 2 H), 7.82 (t, J =7.8 Hz,
1 H), 7.68 (d, J =7.9 Hz, 1 H), 7.53ꢀ 7.37 (m, 4 H), 5.58 (d, J =47.0 Hz,
2 H). 19F NMR (376 MHz, CDCl3) δ -221.22 (t, J =47.0 Hz). 13C NMR
(101 MHz, CDCl3) δ 157.1 (d, J =2.1 Hz), 156.6 (d, J =22.0 Hz), 139.1,
137.7, 129.3, 128.9, 127.1, 119.9, 118.8 (d, J =5.9 Hz), 84.8 (d, J
film)
ν 3100, 2970, 1606, 1500, 1455, 1421, 1357, 1326, 1198, 1166,
1024, 750 cmꢀ 1; MS (EI): m/z 191.0 [M]+; HRMS (EI) m/z: [M]+
Calculated for C11H10FNO: 191.0741; Found: 191.0735.
4.4.11. 6-Bromo-2-(fluoromethyl)quinoline (2k)
=169.7 Hz). IR (thin film)
ν
3063, 2954, 1592, 1578, 1460, 1449, 1358,
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2k was obtained as a yellow solid (69.8 mg,
73 %). M.P. 97ꢀ 99 ◦C. 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J =8.5 Hz,
1 H), 7.95 (d, J =2.2 Hz, 1 H), 7.88 (d, J =9.0 Hz, 1 H), 7.75 (dd,
J = 9.0, 2.2 Hz, 1 H), 7.58 (d, J =8.5 Hz, 1 H), 5.61 (d, J =46.9 Hz,
2 H). 19F NMR (376 MHz, CDCl3) δ -221.96 (t, J =46.9 Hz). 13C NMR
(101 MHz, CDCl3) δ 157.4 (d, J =21.9 Hz), 146.0, 136.2, 133.5, 130.8,
129.8, 128.8, 120.7, 119.1 (d, J =5.2 Hz), 84.8 (d, J =170.7 Hz). IR
1032, 809, 760, 694, 624 cmꢀ 1; MS (EI): m/z 187.0 [M]+; HRMS (EI) m/
z: [M]+ Calculated for C12H10FN: 187.0792; Found: 187.0797.
4.4.6. 2-(Fluoromethyl)-5-phenylpyridine (2f)
After purification by silica gel column chromatography (hexane/
EtOAc = 15:1), compound 2f was obtained as a yellow oil (15.1 mg, 20
%). 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J =2.2 Hz, 1 H), 7.96 (dd,
J = 8.1, 2.3 Hz, 1 H), 7.64ꢀ 7.38 (m, 6 H), 5.55 (d, J =46.9 Hz, 2 H). 19F
NMR (376 MHz,CDCl3) δ -220.26 (t, J =46.9 Hz). 13C NMR (101 MHz,
CDCl3) δ 155.1 (d, J =21.5 Hz), 147.7, 137.5, 136.4, 135.6, 129.3,
128.5, 127.3, 120.9 (d, J =5.5 Hz), 84.4 (d, J =169.7 Hz). IR (thin film)
(thin film)
ν
3030, 2939, 1596, 1493, 1036, 886, 829, 636 cmꢀ 1; MS
(EI): m/z 238.9 [M]+; HRMS (EI) m/z: [M]+ Calculated for C10H7BrFN:
238.9740; Found: 238.9737.
ν
3060, 3031, 2953, 1597, 1480, 1449, 1376, 1031, 1006, 838, 760, 697
4.4.12. 2-(Fluoromethyl)-6-iodoquinoline (2l)
cmꢀ 1; MS (EI): m/z 187.0 [M]+; HRMS (EI) m/z: [M]+ Calculated for
After purification by silica gel column chromatography (hexane/
EtOAc = 15:1), compound 2 L was obtained as a yellow solid (78.2 mg,
68 %). M.P. 111ꢀ 113 ◦C. 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1 H),
8.08 (d, J =8.5 Hz, 1 H), 7.93 (dd, J = 8.9, 2.0 Hz, 1 H), 7.75 (d, J
=8.9 Hz, 1 H), 7.58 (d, J =8.5 Hz, 1 H), 5.61 (d, J =46.9 Hz, 2 H). 19F
NMR (376 MHz, CDCl3) δ -222.08 (t, J =46.8 Hz). 13C NMR (101 MHz,
CDCl3) δ 157.5 (d, J =21.9 Hz), 146.4 (d, J =1.9 Hz), 138.8, 136.6,
136.0, 130.8, 129.4, 118.9 (d, J =5.4 Hz), 92.4, 84.9 (d, J =170.9 Hz).
C12H10FN: 187.0792; Found: 187.0795.
4.4.7. 3,5-Dichloro-2-(fluoromethyl)pyridine (2g)
After purification by silica gel column chromatography (hexane/
EtOAc = 10:1), compound 2 g was obtained as a yellow oil (41.5 mg, 58
%). 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1 H), 7.76 (s, 1 H), 5.55 (d, J
=47.0 Hz, 2 H). 19F NMR (376 MHz, CDCl3) δ -217.90 (t, J =47.0 Hz).
13C NMR (101 MHz, CDCl3) δ 150.4 (d, J =16.0 Hz), 146.7, 137.0 (d, J
=1.6 Hz), 132.7 (d, J =3.4 Hz), 131.8 (d, J =2.3 Hz), 82.0 (d, J
IR (thin film) ν 2950, 1590, 1487, 1386, 1267, 1034, 895, 829, 737, 630
cmꢀ 1; MS (EI): m/z 286.9 [M]+; HRMS (EI) m/z: [M]+ Calculated for
=171.2 Hz). IR (thin film)
ν
3065, 2965, 1566, 1443, 1377, 1118, 1061,
C10H7FIN: 286.9602; Found: 286.9601.
1002, 874, 710, 655 cmꢀ 1; MS (EI): m/z 178.9 [M]+; HRMS (EI) m/z:
5