Quinoline conjugated imidazopyridine and pyridopyrimidine synthesis in water as highly…
Typical synthesis procedure (for example 4a)
yield: 0.335 g (80%); IR (KBr): v=3453 (NH), 3351, 3409
NH ), 2168 (CN), 1654 (C=N), 1590 (C=C), 1355, 1565
(
2
−
1 1
A mixture of 0.19 g 2-chloroquinoline-3-carbaldehyde
(NO ) cm ; H NMR (500 MHz, DMSO-d ): δ=3.90 (m,
2 6
3
3
(
1 mmol) and 0.068 g malononitrile (1 mmol) and 2 cm
2
2H, CH NH), 4.09 (t, J =8.75 Hz, 2H, CH N), 5.33 (s,
2 HH 2
3
3
H O was mixed in a 50 cm round bottom ꢁask at room
1H, CH), 6.65 (s, 2H, NH ), 7.77 (t, J = 3.75 Hz, 2H,
2 HH
3
temperature. After 30 min, 0.06 g ethylenediame (1 mmol)
and 0.165 g nitro ketene dithioacetal (1 mmol) were added to
the reaction mixture, and stirring was allowed to continue at
reꢁux for 3 h. The completion of the reaction was monitored
using thin layer chromatography. After completion of the
reaction the precipitated product was ꢀltered and washed
with cold ethanol to aꢂord the pure product 4a.
CH of Ar), 7.90 (d, J =8.8 Hz, 1H, CH of Ar), 7.97 (d,
HH
3
3
J
=8.8 Hz, 1H, CH of Ar),8.04 (t, J =4 Hz, 1H, CH
HH
HH
3
of Ar), 8.43 (s, 1H, CH of Ar), 8.99 (t, J =5.2 Hz, 1H,
HH
1
3
CH of Ar), 9.66 (s, 1H, NH) ppm; C NMR (125 MHz,
DMSO-d ): δ=39.4 (CH), 43.9 (CH NH), 45.18 (CH N),
6
2
2
66.8 (C–CN), 77.6 (CN), 105.0 (CNO ), 120.9 (CH of Ar),
2
124.0 (CH of Ar), 125.1 (CH of Ar), 126.1 (CH of Ar),
1
27.9 (CH of Ar), 128.51 (CH of Ar), 128.59 (CH of Ar),
5
‑Amino‑7‑(2‑chloroquinolin‑3‑yl)‑8‑nitro‑1,2,3,7‑tet‑
129.2 (CH of Ar),129.9 (C
of Ar), 133.7 (C
ipso
of Ar),
ipso
ipso
ipso
r a h y d r o i m i d a z o [ 1 , 2 ‑ a ] p y r i d i n e ‑ 6 ‑ c a r b o ‑
nitrile (4a, C H ClN O ) Yellow powder; m.p.: 285 °C
139.2 (C
of Ar), 144.3 ( 2C
of Ar), 148.8 (C -N),
ipso
150.2 (C of Ar), 152.3 (C–NH ) ppm.
1
7
15
6
2
ipso
2
(
decomp); yield: 0.331 g (90%); IR (KBr): v =3433 (NH),
3
1
377, 3298 (NH ), 2172 (CN), 1659 (C=N), 1586 (C=C),
6‑Amino‑8‑(3‑chloro‑7‑methylnaphthalen‑2‑yl)‑9‑ni‑
tro‑1,3,4,8‑tetrahydro‑2H‑pyrido[1,2‑a]pyrimidine‑7‑car‑
bonitrile (5a, C H ClN O ) Yellow powder; m.p.: 281 °C
2
−
1
472, 1377 (NO ) cm ; MS (EI, 70 eV): m/z (%) = 369
2
+
1
(
M -1, 3), 313 (6), 239 (9), 177 (5), 57 (58), 43 (100); H
1
9
19
6 2
NMR (500 MHz, DMSO-d ): δ = 3.86 (m, 2H, CH NH),
(decomp); yield: 0.309 g (78%); IR (KBr): v=3395, 3342
6
2
4
7
1
.06 (m, 2H, CH N), 5.25 (s, 1H, CH), 6.62 (s, 2H, NH ),
(NH ), 3231 (NH), 2179 (CN), 1659 (C=N), 1630 (C=C),
2
2
2
3
3
−1 1
.62 (t, J =7.5 Hz, 1H, CH of Ar), 7.77 (t, J =8 Hz,
1495, 1346 (NO ) cm ; H NMR (500 MHz, DMSO-d ):
HH
HH
2
6
3
H, CH of Ar), 7.92 (d, J =8.35 Hz, 1H, CH of Ar), 8.01
δ=2.03–2.07 (m, 1H, CH ), 2.13–2.17 (m, 1H, CH ), 2.47
HH
2
2
3
(
d, J =8.5 Hz, 1H, CH of Ar), 8.36 (s, 1H, H of Ar), 9.64
(s, 3H, CH ), 3.41–3.45 (m, 1H, CH NH), 3.65–3.69 (m,
3 2
HH
1
3
(
s, 1H, NH) ppm; C NMR (125 MHz, DMSO-d ): δ=39.9
1H, CH NH), 3.74–3.79 (m, 1H, CH N), 3.85–3.89 (m,
2 2
6
(
CH), 43.8 (CH ), 45.1 (CH ), 57.4 (C–CN), 105.3 (CN),
1H, CH N), 5.24 (s, 1H, CH), 6.54 (s, 2H, NH ), 7.60 (d,
2 2
2
2
3
3
1
20.8 (C–NO ), 127.6 (CH of Ar), 127.8 (CH of Ar), 127.9
J
=8.55 Hz, 1H, CH of Ar), 7.80 (d, J =3.45 Hz, 2H,
HH HH
2
(CH of Ar), 128.0 (CH of Ar), 130.8 (CH of Ar), 138.6 (C
CH of Ar), 7.82 (s, 1H, CH of Ar), 8.12 (s, 1H, CH of Ar),
ipso
1
3
of Ar), 146.3 (C -N and C of Ar), 149.9 (C of Ar),
11.75 (s, 1H, NH) ppm; C NMR (125 MHz, DMSO-d ):
ipso
ipso
ipso
6
1
50.2 (C of Ar), 152.2 (C–NH ) ppm.
δ=19.9 (CH ), 21.5 (CH ), 38.3 (CH), 38.8 (CH NH), 43.6
ipso
2
2
3
2
(
CH N), 59.2 (C–CN), 107.6 (CN), 120.7 (C–NO ), 126.9
2
2
5
‑Amino‑7‑(2‑chloro‑6‑methylquinolin‑3‑yl)‑8‑ni‑
(CH of Ar), 127.5 (CH of Ar), 127.7 (CH of Ar), 133.0 (CH
of Ar), 136.2 (C of Ar), 137.2 (C of Ar), 137.4 (C
tro‑1,2,3,7‑tetrahydroimidazo[1,2‑a]pyridine‑6‑carbo‑
nitrile (4b, C H ClN O ) Yellow powder; m.p.: 297 °C
ipso
ipso
ipso
of Ar), 144.9 (C -N), 148.7 (C of Ar), 151.1 (C of
1
8
17
6
2
ipso
ipso
ipso
(
decomp); yield: 0.317 g (83%); IR (KBr): v=3434 (NH),
Ar), 151.8 (C–NH ) ppm.
2
3
1
371, 3300 (NH ), 2173 (CN), 1658 (C=N, C=C), 1475,
2
−
1 1
346 (NO ) cm ; H NMR (500 MHz, DMSO-d ): δ=2.46
6‑Amino‑8‑(3‑chloro‑7‑methylnaphthalen‑2‑yl)‑3,3‑di‑
methyl‑9‑nitro‑1,3,4,8‑tetrahydro‑2H‑pyrido[1,2‑a]pyrim‑
idine‑7‑carbonitrile (5b, C H ClN O ) Yellow powder;
2
6
3
(
s, 3H, CH ), 3.85 (t, J =8.3 Hz, 2H, CH NH), 4.05 (t,
3 HH 2
3
J
= 10 Hz, 2H, CH N), 5.20 (s, 1H, CH), 6.59 (s, 2H,
HH
2
21 23
6 2
3
NH ), 7.58 (d, J =8.8 Hz, 1H, CH of Ar), 7.75 (s, 1H,
m.p.: 283 °C (decomp); yield: 0.305 g (72%); IR (KBr):
2
HH
3
CH of Ar), 7. 79 (d, J =8.65 Hz, 1H, CH of Ar), 8.22 (s,
v=3392, 3322 (NH ), 3187 (NH), 2184 (CN), 1664 (C=N),
HH
2
13
−1 1
1
H, CH of Ar), 9.61 (s, 1H, NH) ppm; C NMR (125 MHz,
1628 (C=C), 1540, 1339 (NO ) cm ; H NMR (500 MHz,
2
DMSO-d ): δ = 21.5 (CH ), 39.9 (CH), 43.8 (CH ), 45.1
DMSO-d ): δ=1.08 (s, 3H, CH ), 1.12 (s, 3H, CH ), 2.48
6
3
2
6
3
3
3
(
CH ), 57.6 (C–CN), 95.3 (CN), 104.7 (C–NO ), 120.8 (CH
(s, 3H, CH ), 3.25 (d, J = 13.4 Hz, 2H, CH NH), 3.54
2
2
3 HH 2
3
3
of Ar), 126.7 (CH of Ar), 127.5 (CH of Ar), 127.8 (CH of
(d, J =12.25 Hz, 1H, CH N), 3.62 (d, J =12.15 Hz,
HH 2 HH
Ar), 132.9 (C of Ar), 137.2 (C of Ar), 138.0 (C of
1H, CH N), 5.13 (s, 1H, CH), 6.51 (s, 2H, NH ), 7.62 (d,
ipso
ipso
ipso
2
2
3
Ar), 144.9 (C -N), 148.9 (C of Ar), 150.2 (C of Ar),
J
=8.55 Hz, 1H, CH of Ar), 7.73 (s, 1H, CH of Ar), 7.83
ipso
ipso
ipso
HH
3
1
52.2 (C–NH ) ppm.
(d, J =8.65 Hz, 1H, CH of Ar), 8.08 (s, 1H, CH of Ar),
2
HH
1
3
1
1.72 (s, 1H, NH) ppm; C NMR (125 MHz, DMSO-d ):
6
5
1
‑Amino‑7‑(2‑chlorobenzo[h]quinolin‑3‑yl)‑8‑nitro‑
,2,3,7‑ tetrahydroimidazo[1,2‑a]pyridine‑6‑carbonitrile
δ = 21.5 (CH ), 23.6 (CH ), 24.1 (CH ), 27.5 (CH), 38.8
3 3 3
(C(CH ) ), 49.6 (CH ), 53.2 (CH ), 59.4 (C–CN), 107.2
3
2
2
2
(
4c, C H ClN O ) Orange powder; m.p.: 268 °C (decomp);
(CN), 120.6 (C–NO ), 126.7 (CH of Ar), 127.6 (CH of Ar),
2
1
17
6
2
2
1
3