4
2
M. C. Kimber et al.
5
-Methoxy-2-nitroaniline (4)
6.17 mmol) was then added gradually and the mixture stirred at room
temperature overnight. The reaction mixture was then poured onto ice
and the precipitate extracted with ethyl acetate. Removal of the solvent
followed by chromatography yielded the nitroquinoline (9) as a yellow
[
29]
The title compound was prepared using a literature procedure to yield
◦
[29]
◦
m.p. 126–128 C,
a yellow solid (2.0 g, 71%), m.p. 127.5–129 C (lit.
RF 0.50 CH2Cl2). δH (300 MHz; CDCl3) 8.05 (1 H, d, J3,4 9.5, H3),
.23 (1 H, dd, J3,4 9.5, J4,6 3.9, H4), 6.18 (2 H, br s, NH2), 6.12 (1 H,
◦
[33]
◦
solid (0.560 g, 56%), m.p. 112–114 C (lit.
m.p. 111–113 C, RF 0.80
6
CH2Cl2). δH (300 MHz; CDCl3) 8.33 (1 H, dd, J5,7 1.4, J6,7 8.5, H7),
7.95 (1 H, dd, J5,6 7.4, J5,7 1.4, H5), 7.63–7.55 (1 H, dd, J5,6 7.3, J6,7
d, J4,6 3.9, H6), 3.81 (3 H, s, OCH3). Mass spectrum m/z 168 (100%,
M
+
•
+•
+•
), 138 (58, [M – CH2O] ), 122 (32, [M – NO2] ), 110 (24), 107
+
•
8
1
4
.5, H6), 2.71 (3 H, s, CH3). Mass spectrum m/z 222 (100%, M ),
92 (28), 176 (29), 164 (98), 140 (66), 114 (31), 74 (32), 63 (33),
6 (80).
(
19), 95 (32), 79 (35), 52(44).
5
-Methoxy-2-methyl-8-nitroquinoline (5)
5
-Methoxy-2-nitroaniline (4) (0.50 g, 2.98 mmol), paraldehyde (0.80 g),
4
-Methoxy-2-methyl-8-nitroquinoline (10)
and concentrated hydrochloric acid (2.9 mL) were refluxed for 3.5 h
with vigorous stirring. The mixture was then cooled, neutralized with
concentrated sodium hydroxide and the aqueous layer extracted
with dichloromethane (2×100 mL). The organic extract was washed
with water (2×50 mL), dried and the solvent removed under vacuum.
The crude mixture was chromatographed (dichloromethane) yielding
4-Chloro-2-methyl-8-nitroquinoline (9) (0.300 g, 1.33 mmol) was
stirred in a solution of sodium (0.06 g, 2.61 mmol) in methanol (3 mL)
and the mixture was refluxed under nitrogen for 2 h. The reaction was
then cooled, the solvent was removed under reduced pressure, and
the residue was dissolved in dichloromethane and purified by flash
chromatography to give the ether as white needles (0.200 g, 68%), m.p.
◦
the required product as an orange solid (0.150 g, 25%), m.p. 112–114 C
RF 0.32 CH2Cl2). δH (300 MHz; CDCl3) 8.30 (1 H, d, J6,7 8.6, H7),
◦
[33] ◦
(
130–131 C (lit.
m.p. 129–130 C, RF 0.45 CH2Cl2). δH (300 MHz;
7
8
2
.95 (1 H, d, J3,4 8.5, H4), 7.23 (1 H, d, J6,7 8.6, H6), 6.63 (1 H, d, J3,4
CDCl3) 8.27 (1 H, dd, J5,7 1.4, J6,7 8.4, H7), 7.88 (1 H, dd, J5,6 7.5,
J5,7 1.4, H5), 7.46–7.38 (1 H, dd, J5,6 7.5, J6,7 8.4, H6), 6.68 (1 H, s,
H3), 4.02 (3 H, s, OCH3), 2.66 (3 H, s, CH3). Mass spectrum m/z 218
.5, H3), 3.94 (3 H, s, OCH3), 2.64 (3 H, s, CH3). Mass spectrum m/z
+
•
+•
18 (88%, M ), 188 (100, [M – CH2O] ), 173 (72), 160 (46), 145
+
•
(
48), 91 (50), 69 (55), 57 (53), 42 (72).
(100%, M ), 188 (26), 172 (24), 159 (45), 130 (61), 89 (44), 69 (40),
5
7 (45), 43 (80).
8
-Amino-5-methoxy-2-methylquinoline (6)
8
-Amino-6-methoxy-2-methylquinoline (11)
5
-Methoxy-2-methyl-8-nitroquinoline (5) (100 mg, 0.459 mmol) was
refluxed in the presence of iron powder (50 mg), acetic acid (1 mL),
and ethanol (10 mL) for 4 h under a nitrogen atmosphere. The reaction
mixture was cooled, poured into water (50 mL) and the solution was
extracted with dichloromethane (100 mL). The organic layer was dried,
filtered and the solvent removed under reduced pressure to yield the title
compound as an orange-brown oil (71.0 mg, 82%) which was used with-
out further purification. δH (300 MHz; CDCl3) 8.35 (1 H, d, J6,7 8.5,
H7), 7.21 (1 H, d, J6,7 8.5, H6), 6.80 (1 H, d, J3,4 8.2, H4), 6.62 (1 H, d,
J3,4 8.2, H3), 4.60 (2 H, br s, NH2), 3.88 (3 H, s, OCH3), 2.67 (3 H, s,
Nitroquinoline (10) (0.185 g, 0.85 mmol) was reduced under iron/acetic
acid conditions as stated above for the formation of (6). The amine (11)
was obtained as a yellow crystalline solid (0.153 g, 96%), m.p. 113–
◦
[33,34]
◦
115 C (lit.
m.p. 113–116 C). δH (300 MHz; CDCl ) 7.35 (1 H,
3
dd, J5,7 1.4, J6,7 8.4, H7), 7.12 (1 H, dd, J5,6 7.5, J6,7 8.4, H6), 6.81–
6.77 (1 H, dd, J5,6 7.5, J5,7 8.4, H5), 6.47 (1 H, s, H3), 4.78 (2 H, br s,
NH ), 3.87 (3 H, s, OCH ), 2.56 (3 H, s, CH ). Mass spectrum m/z 188
2
3
3
+
•
(100%, M ), 118 (16).
+
•
+•
CH3). Mass spectrum m/z 188 (71%, M ), 173 (100, [M – CH3] ),
N-(4-Methoxy-2-methyl-8-quinolyl)-(4-methylbenzene)
sulfonamide (12)
1
45(24).
N-(5-Methoxy-2-methyl-8-quinolyl)-(4-methylbenzene)
sulfonamide (7)
The amine (11) (0.150 g, 0.79 mmol) was tosylated under standard
[
12]
conditions. The required product was obtained as pale yellow prisms
◦
(
0.249 g, 90%), m.p. 191–193 C (Found: C, 63.2; H, 5.1; N, 8.4%.
The amine (6) (71 mg, 0.378 mmol) was tosylated using standard
−1
C18H18N2O3S requires C, 63.1; H, 5.3; N, 8.2%). υmax/cm 3270,
[12]
conditions
to yield the title compound as pale yellow crystals
1
7
600, 1510, 1350, 1170. δH (300 MHz; CDCl3) 9.28 (1 H, br s, NH),
after recrystallization from dichloromethane/hexane (97 mg, 75%), m.p.
ꢀ
.79–7.74 (2 H, d, J2ꢀ,3ꢀ 8.2, H2 ), 7.22–7.65 (2 H, m, H5,7), 7.29–7.21
◦
1
62–164 C (Found: C, 62.9; H, 5.1; N, 8.1%. C18H18N2O3S requires C,
ꢀ
(
(
1 H, dd, J5,6 7.6, J6,7 8.6, H6), 7.14–7.09 (2 H, d, J2ꢀ,3ꢀ 8.2, H3 ), 5.57
6
3.1; H, 5.3; N, 8.2%). δH (300 MHz; CDCl3) 8.88 (1 H, br s, NH), 8.33
1 H, s, H3), 3.95 (3 H, s, OCH3), 2.51 (3 H, s, CH3), 2.27 (3 H, s,
ꢀ
(
1 H, d, J6,7 8.6, H7), 7.72–7.69 (3 H, m, H2 ,4), 7.22 (1 H, d, J6,7 8.6,
+•
ArCH3). Mass spectrum m/z 342 (52%, M ), 293 (70), 278 (25), 187
ꢀ
H6), 7.08 (2 H, d, J2ꢀ,3ꢀ 8.4, H3 ), 6.68 (1 H, d, J3,4 8.4, H3), 3.92 (3 H,
+•
(
100, [M – C7H7SO2] ), 137 (97), 123 (33), 91 (50), 69 (40). Crystals
s, OCH3), 2.64 (3 H, s, CH3), 2.26 (3 H, s,ArCH3). Mass spectrum m/z
suitable for X-ray analysis were obtained from CH2Cl2/hexane.
+
•
+•
3
42 (26%, M ), 242 (30), 187 (95, [M – C7H7SO2] ), 121 (68), 105
(
50), 91 (32), 65 (100).
2
-Chloro-8-nitroquinoline (14)
4
-Chloro-2-methylquinoline (8)
Thetitlecompoundwaspreparedfrom4-hydroxy-2-methylquinoline
1.5 g, 9.4 mmol) by refluxing in phosphorous oxychloride (5 mL) for
h with vigorous stirring. The reaction was then cooled, poured onto
2-Chloroquinoline (13) (1.00 g, 6.1 mmol) was nitrated using the same
conditions as for the formation of 4-chloro-2-methyl-8-nitroquinoline
[
31]
(
(
9). This yielded the required nitroquinoline after chromatography
dichloromethane), which was then recrystallized from ethanol to give
(
3
2
1
-chloro-8-nitroquinoline (14) as yellow needles (0.620 g, 49%), m.p.
crushed ice and neutralized with 25% aqueous sodium hydroxide. The
yellow oil which formed was collected and purified by chromatography
to afford the chloroquinoline (8) as the monohydrate (0.900 g, 81%),
◦
[35,36]
◦
48–149 C (lit.
m.p. 148–149 C). δH (300 MHz; CDCl3) 8.17
(
1 H, d, J3,4 8.6, H4), 8.09–8.00 (2 H, m, H5,7), 7.66–7.58 (1 H, dd, J5,6
◦
[40]
◦
m.p. 42–44 C). δH (300 MHz; CDCl3) 8.15 (1 H,
8.3, J6,7 7.5, H6), 7.52 (1 H, d, J 8.6, H3). Mass spectrum m/z 208
3,4
m.p. 40–42 C (lit.
dd, J 8.4 and 1.4, H8), 8.00 (1 H, m, H5), 7.75–7.66 (1 H, m, H7), 7.59–
.50 (1 H, m, H6), 7.37 (1 H, s, H3), 2.70 (3 H, s, CH3). Mass spectrum
+
•
(
100%, M ), 192 (20), 178 (53), 156 (83), 127 (72).
7
+
•
m/z 177 (30%, M ), 140 (91), 99 (41), 74 (36), 62 (40), 49 (100),
2-Methoxy-8-nitroquinoline (15)
4
3 (82).
The title compound was prepared using the same procedure used for
the formation of 4-methoxy-2-methyl-8-nitroquinoline (10) to yield
4
-Chloro-2-methyl-8-nitroquinoline (9)
◦
[34]
a white solid (265 mg, 90%), m.p. 126.5–128 C (lit.
m.p. 122–
◦
4
-Chloro-2-methylquinoline (8) (0.800 g, 4.52 mmol) was dissolved in
123 C). δH (300 MHz; CDCl3) 8.00 (1 H, d, J3,4 8.9, H4), 7.93 (1 H,
dd, J5,7 1.5, J6,7 8.0, H7), 7.86 (1 H, dd, J5,6 8.0, J5,7 1.4, H5),
◦
sulfuric acid (2.90 mL) and stirred at 0 C. Potassium nitrate (0.625 g,