January 2016
Synthesis of Butyl 8-Aminoquinolines
269
using dichloromethane (3 × 100 mL), dried over anhydrous
149.26, 152.31 ppm; HRMS (ESI): (m/z) calcd. for
+
Na SO4 and filtered. Solvent was removed on a rotary
C H N O [M + H] : 231.1134, found: 231.1128.
2
13 15 2 2
À1
evaporator. The crude products were subjected to column
chromatography using silica and different solvent mixtures, but
the vast majority of the products were inseparable. In order to
identify the structures of 5-butylquinoline 17 and 7-
butylquinoline 18, a small amount of mixture was separated by
7-butyl-8-nitroquinoline (21).
mp 42°C; FTIR (v, cm ):
2957, 2930, 2872, 1598, 1529, 1497, 1457, 1376, 1354, 1315,
1
3
876, 838, 799, 642; H-NMR (CDCl ), δ: 0.92 (t, 3H,
J = 7.2 Hz), 1.39 (m, 2H), 1.68 (m, 2H), 2.75 (t, 2H, J = 7.6 Hz),
7.44 (d, 1H, J = 8.0 Hz), 7.46 (t, 1H, J = 8.0, 4.4 Hz), 7.84 (d,
analytical chromatography on silica TLC plates. The amount of
1H, J = 8.8 Hz), 8.16 (dd, 1H, J = 8.8, 1.6 Hz), 8.93 (dd, 1H,
J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl ), δ: 13.77, 22.53, 31.34,
3
1
13
5
-butylquinoline 17 was just enough to obtain H-NMR.
Because it was difficult to separate isomers, the mixture of
32.67, 122.11, 126.91, 127.91, 129.24, 134.76, 135.62, 139.67,
products was nitrated at the next step, 6.82 g (72%);
148.10, 152.06 ppm; HRMS (ESI): (m/z) calcd. for C H N O
[M + H] : 231.1134, found: 231.1106.
1
3 15 2 2
+
regioisomeric ratio 1:4.
1
5
-butylquinoline (17).
3
H-NMR (CDCl ), δ: 0.85 (t, 3H,
8-amino-5-butylquinoline (22).
experiment is the same as 4 (96.4%); FTIR (v, cm ): 3465,
The procedure of this
À1
J= 7.6 Hz), 1.33 (m, 2H), 1.58 (m, 2H), 2.92 (t, 2H, J=7.6Hz),
,25 (d, 1H, J= 6.8 Hz), 7.28 (t, 1H, J= 8.0, 4.0 Hz), 7.50 (dd, 1H,
J= 8.4, 6.8 Hz), 7.87 (d, 1H, J= 8.8 Hz), 8.23 (dd, 1H, J=8.0,
.6 Hz), 8.78 (dd, 1H, J= 4.0, 1.6 Hz) ppm; HRMS (ESI): (m/z)
7
3353, 2953, 2927, 2857, 1610, 1587, 1506, 1477, 1365, 1336,
1
821, 785; H-NMR (CDCl ), δ: 0.97 (t, 3H, J = 7.6 Hz), 1.44
3
1
(m, 2H), 1.66 (m, 2H), 2.92 (t, 2H, J = 7.6 Hz), 4.87 (bs, 2H)
6.86 (d, 1H, J = 7.6 Hz), 7.16 (d, 1H, J = 7.6 Hz), 7.35 (dd, 1H,
J = 8.8, 4.4 Hz), 8.26 (dd, 1H, J = 8.8, 1.6 Hz), 8.78 (dd, 1H,
+
calcd. for C13
H
16N [M+H] : 186.1283, found: 186.1263.
À1
7
-butylquinoline (18). FTIR (v, cm ): 3049, 2955, 2928,
13
2
858, 1625, 1596, 1501, 1450, 1317, 833, 769, 730, 614, 477;
J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl ), δ: 14.06, 22.73, 31.54,
3
1
H-NMR (CDCl ), δ: 0.94 (t, 3H, J = 7.2 Hz), 1.39 (m, 2H),
33.45, 109.89, 120.77, 126.90, 127.28, 132.43, 138.97, 142.28,
3
+
1
4
7
.70 (m, 2H), 2.82 (t, 2H, J = 7.6 Hz), 7,32 (dd, 1H, J = 8.4,
.4 Hz), 7.38 (dd, 1H, J = 8.4, 1.6 Hz), 7.71 (d, 1H, J = 8.4 Hz),
.88 (s, 1H), 8.09 (dd, 1H, J = 8.0, 1.2 Hz), 8.67 (dd, 1H,
146.82 ppm; HRMS (ESI): (m/z) calcd. for C13
H
17
N
2
[M + H] :
201.1392, found: 201.1376.
8-amino-7-butylquinoline (23).
experiment is the same as 4 (75%); FTIR (v, cm ): 3478,
The procedure of this
1
3
À1
J = 4.0, 1.6 Hz) ppm; C-NMR (CDCl ), δ: 13.92, 22.29, 33.14,
3
3
1
5.80, 120.29, 126.55, 127.44, 127.73, 128.21, 135.78, 144.70,
3370, 3050, 2954, 2927, 2858, 1586, 1558, 1504, 1456, 1371,
1
48.43, 150.23 ppm; HRMS (ESI): (m/z) calcd. for C13
H
16
N
1105, 822, 798, 673; H-NMR (CDCl
3
), δ: 1.00 (t, 3H,
+
[
M + H] : 186.1283, found: 186.1263.
Nitration of 5-butylquinoline (17) and 7-butylquinoline (18)
mixture. To a mixture of 17 and 18 (6.82 g, 36.81 mmol) in
5.5 mL concentrated H SO , cooled in an iced bath was added
dropwise 12.5 mL of concentrated H SO /HNO mixture (3:1).
J = 7.6 Hz), 1.47 (m, 2H), 1.71 (m, 2H), 2.71 (t, 2H, J = 7.2 Hz),
5.02 (bs, 2H), 7.13 (d, 1H, J = 8.4 Hz), 7.28 (d, 1H, J = 8.4 Hz),
7.30 (t, 1H, J = 8.0, 4.0 Hz), 8.01 (d, 1H, J = 8.4 Hz), 8.77 (d,
13
1
2
4
1H, J = 4.0 Hz) ppm; C-NMR (CDCl
3
), δ: 14.10, 22.85, 31.01,
2
4
3
31.44, 115.44, 120.44, 122.74, 127.15, 129.16, 135.82, 138.43,
Reaction was maintained at 0°C, stirred rapidly and monitored
by TLC until all the quinoline was consumed (2.5 h). Mixture
was diluted with 50 mL water, and NaOH(s) was added until
140.71, 147.37 ppm; HRMS (ESI): (m/z) calcd. for C13
[M + H] : 201.1392, found: 201.1367.
H
17
N
2
+
6-butylquinoline (24).
the same as with 17 and 18 (59%); FTIR (v, cm ): 3013, 2955,
The procedure of this experiment is
À1
pH 10–11. Solution was extracted with 3 × 100 mL CH
2
Cl
2
,
dried over anhydrous Na SO , filtered and evaporated. Nitration
2
4
2927, 2856, 1499, 1464, 1377, 1118, 833, 796, 770, 615, 478;
H-NMR (CDCl ), δ: 0.86 (t, 3H, J = 7.2 Hz), 1.31 (m, 2H), 1.60
3
(m, 2H), 2.69 (t, 2H, J = 7.6 Hz), 7.23 (dd, 1H, J = 8.4, 4.4 Hz),
1
of 17 and 18 resulted in 5-butyl-8-nitroquinoline 20, 5-butyl-6-
nitroquinoline 19, and 7-butyl-8-nitroquinoline 21. In order to
separate the mixture of isomers, the column was prepared using
silica gel and dichloromethane/hexane (3:1) as the eluent phase.
7.46 (m, 2H), 7.93 (d, 1H, J = 9.2 Hz), 7.95 (d, 1H, J = 8.4 Hz),
13
3
8.74 (dd, 1H, J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl ), δ: 12.89,
5
-butyl-8-nitroquinoline 20, 1.13 g (13%); 5-butyl-6-
21.32, 32.33, 34.55, 119.96, 124.96, 127.30, 128.13, 130.03,
nitroquinoline 19, 0.1 g (1.2%); 7-butyl-8-nitroquinoline 21,
134.48, 140.27, 146.07, 148.47ppm; HRMS (ESI): (m/z) calcd.
+
7
.45 g (86%); overall nitration yield: 90%.
-butyl-8-nitroquinoline (20). mp 73°C; FTIR (v, cm ):
079, 2954, 2927, 2868, 2359, 1574, 1515, 1468, 1397, 836,
for C H N [M+ H] : 186.1283, found: 186.1278.
13 16
À1
5
6-butyl-5-nitroquinoline (25).
The procedure of this
3
7
experiment is the same as with 3. Brown viscous liquid (62%);
1
À1
97, 773, 740, 635, 613, 487; H-NMR (CDCl
3
), δ: 0.98 (t, 3H,
FTIR (v, cm ): 2958, 2931, 2872, 1522, 1495, 1464, 1353,
1
J = 7.6 Hz), 1.46 (m, 2H), 1.71 (m, 2H), 3.10 (t, 2H, J = 8.0 Hz),
1328, 877, 838, 812, 797, 770, 746, 542; H-NMR (CDCl ), δ:
3
7
1
.42 (d, 1H, J = 7.6 Hz), 7.55 (dd, 1H, J = 8.4, 4.0 Hz), 7.94 (d,
H, J = 7.6 Hz), 8.43 (dd, 1H, J = 8.8, 1.6 Hz), 9.05 (dd, 1H,
0.83 (t, 3H, J = 7.2 Hz), 1.29 (m, 2H), 1.59 (m, 2H), 2.67 (t, 2H,
J = 7.6 Hz), 7.42 (dd, 1H, J = 8.0, 4.4, 1.6 Hz), 7.52 (d, 1H,
J = 8.8 Hz), 7.93 (d, 1H, J = 8.8 Hz), 8.06 (d, 1H, J = 8.8 Hz),
8.84 (dd, 1H, J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl ), δ: 13.75,
3
22.52, 31.54, 32.75, 120.22, 123.05, 130.00, 130.79, 132.18,
1
3
J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl
3
), δ: 13.81, 22.62,
2.32, 32.94, 122.19, 123.49, 124.74, 132.44, 140.03, 144.90,
46.91, 151.91 ppm; HRMS (ESI): (m/z) calcd. for
13
3
1
+
C H N O [M + H] : 231.1134, found: 231.1126.
133.25, 146.36, 146.54, 150.93 ppm; HRMS (ESI): (m/z) calcd.
13
15 2 2
À1
+
5
-butyl-6-nitroquinoline (19).
mp 62°C; FTIR (v, cm ):
for C13H
15
N
2
O
2
[M + H] : 231.1134, found: 231.1123.
2
8
958, 2930, 2872, 1522, 1495, 1464, 1353, 1328, 877, 838,
5-bromo-6-butylquinoline (27) [34]: 24.
18.4 mmol) was slowly added to 18.4 mL concentrated H
(3.42 g,
SO
1
12, 797, 770, 746, 542; H-NMR (CDCl
3
), δ: 1.00 (t, 3H,
2
4
J = 7.6 Hz), 1.55 (m, 2H), 1.75 (m, 2H), 3.18 (t, 2H, J = 8.0 Hz),
dropwise. The exothermic reaction was kept below 30°C, then
the solution was cooled to À40°C, and N-bromosuccinimide
(NBS) (3.83 g, 21.5 mmol) was slowly added to this solution
piecewise while the temperature was kept around À40°C. The
suspension was stirred at 0°C for 1 h. Then the mixture was
7
1
.57 (dd, 1H, J = 8.4, 4.0 Hz), 7.99 (d, 1H, J = 9.2 Hz), 8.05 (d,
H, J = 9.2 Hz), 8.50 (dd, 1H, J = 8.8, 0.8 Hz), 9.03 (dd, 1H,
1
3
J = 4.4, 1.6 Hz) ppm; C-NMR (CDCl
3
), δ: 13.75, 23.13,
2
7.76, 33.27, 122.34, 124.02, 127.00, 129.34, 133.97, 135.01,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet