Reaction of Chloronitrobenzenes with Secondary Amines
General Procedure: Tables 2 and 3. To an oven-dried Schlenk tube
ppm. GC–MS: m/z = 192, 191, 176, 162, 145, 136, 117, 106, 90,
that was flushed with argon, chloronitrobenzene (1.0 mmol), cyclic
77.
secondary amine (1–2 mmol), KHCO
ride (20 mol-%), phosphane ligand (20 mol-%), and p-xylene
0.5 mL) were consecutively added. The mixture was stirred in an
oil bath at 140 °C for 1–4 h. Isolation was achieved by column
chromatography on silica gel, alumina or preparative TLC (hexane/
diethyl ether, dichloromethane or acetone). Products were iden-
tified by NMR, GC–MS, micrOTOF mass and elemental analyses.
3
(1 mmol), cobalt(II) chlo-
1
-Nitro-2-pyrrolidinobenzene: Table 3, Entry 1. Synthesized from 1-
chloro-2-nitrobenzene (0.157 g, 1 mmol) and pyrrolidine
(
(
(
0.164 mL, 2 mmol). The product was isolated as a yellow oil
0.158 g, 82%) after alumina gel column chromatography (hexane/
1
dichloromethane). H NMR (270 MHz, CDCl
3
, 25 °C): δ = 1.98
), 6.70 (ddd, J = 7.2, 6.4,
.0 Hz, 1 H, ArH), 6.90 (d, J = 8.3 Hz, 1 H, ArH), 7.35 (ddd, J =
5.6, 5.1, 1.6 Hz, 1 H, ArH), 7.74 (dd, J = 6.4, 1.6 Hz, 1 H, ArH)
2 2
(m, 4 H, CH ), 3.21 (m, 4 H, NCH
1
1
-Nitro-4-piperidinobenzene: Table 2, Entry 1. Synthesized from 1-
chloro-4-nitrobenzene (0.157 g, 1 mmol) and piperidine (0.198 mL,
mmol). The product was isolated as a yellow solid (0.097 g, 47%)
1
3
ppm. C NMR (67.8 MHz, CDCl
(NCH ), 115.3 (CH), 115.8 (CH), 126.6 (CH), 132.9 (CH), 137.0
(CNCH ), 142.7 (CNO ) ppm. GC–MS: m/z = 192, 175, 157, 145,
117, 104, 91, 77.
3 2
, 25 °C): δ = 25.6 (CH ), 50.3
2
2
1
after silica gel column chromatography (hexane/diethyl ether). H
NMR (270 MHz, CDCl , 25 °C): δ = 1.66 (s, 6 H, CH ), 3.42 (s, 4
H, NCH ), 6.76 (d, J = 7.2 Hz, 2 H, ArH), 8.06 (d, J = 7.5 Hz, 2
H, ArH) ppm. 13C NMR (67.8 MHz, CDCl
, 25 °C): δ = 24.1
), 112.1 (CH), 126.1 (CH), 137.2
) ppm. GC–MS: m/z = 205, 176, 165, 159,
2
2
3
2
2
4-Chloro-2-pyrrolidino-1-nitrobenzene: Table 3, Entry 2. Synthe-
3
sized from 2,4-dichloro-1-nitrobenzene (0.192 g, 1 mmol) and pyr-
rolidine (0.164 mL, 2 mmol). The product was isolated as a yellow
solid (0.205 g, 90%) after alumina gel column chromatography
(CH
2
), 25.1 (CH
), 154.7 (CNCH
2 2
), 48.2 (NCH
(CNO
2
2
150, 131, 120, 103, 91, 77.
1
(
hexane/dichloromethane). H NMR (270 MHz, CDCl
3
, 25 °C): δ
), 6.66 (dd, J = 6.7,
1.89 Hz, 1 H, ArH), 6.89 (d, J = 1.8 Hz, 1 H, ArH), 7.68 (d, J =
1-Nitro-4-[1,2,3,4-tetrahydroisoquinolino]benzene: Table 2, Entry 2.
2 2
= 1.99 (m, 4 H, CH ), 3.20 (m, 4 H, NCH
Synthesized from 1-chloro-4-nitrobenzene (0.157 g, 1 mmol) and
,2,3,4-tetrahydroisoquinoline (0.250 mL, 2 mmol). The product
was isolated as a yellow solid (0.134 g, 53%) after silica gel column
1
3
1
8.6 Hz, 1 H, ArH) ppm. C NMR (67.8 MHz, CDCl
25.6 (CH ), 50.5 (NCH ), 115.4 (CH), 115.5 (CH), 127.9 (CH),
135.3 (CNO ), 139.0 (CCl), 143.1 (CNCH ) ppm. GC–MS: m/z =
), 4.58 226, 209, 180, 178, 153, 138, 111, 89, 75.
), 6.82 [d, J = 9.4 Hz, 2 H, ArH (benzene)], 7.26
m, 4 H, ArH (isoquinoline)], 8.17 [d, J = 9.4 Hz, 2 H, ArH (benz-
3
, 25 °C): δ =
2
2
1
chromatography (hexane/diethyl ether).
CDCl , 25 °C): δ = 3.03 (m, 2 H, CH ), 3.70 (m, 2 H, NCH
m, 2 H, NCH
H
NMR (270 MHz,
2
2
3
2
2
(
[
2
2-Chloro-1-pyrrolidino-4-nitrobenzene: Table 3, Entry 3. Synthe-
sized from 1,2-dichloro-4-nitrobenzene (0.192 g, 1 mmol) and pyr-
rolidine (0.164 mL, 2 mmol). The product was isolated as a yellow
solid (0.117 g, 51%) after preparative TLC (hexane/dichlorometh-
13
ene)] ppm. C NMR (67.8 MHz, CDCl
3
, 25 °C): δ = 28.9 (CH
), 111.1 (CH), 126.1 (CH), 126.4 (CH),
26.6 (CH), 127.13 (CH), 128.05 (CH), 132.90 (C), 134.95 (C),
37.4 (CNO ), 153.9 (CNCH ) ppm. GC–MS: m/z = 254, 253, 207,
65, 127, 115, 104, 91, 78.
2
),
4
1
1
1
2 2
4.7 (NCH ), 48.7 (NCH
1
ane). H NMR (270 MHz, CDCl
3
, 25 °C): δ = 2.00 (s, 4 H, CH
2
),
2
2
3
9
.65 (s, 4 H, NCH
.1 Hz, 1 H, ArH), 8.17 (s, 1 H, ArH) ppm. C NMR (67.8 MHz,
, 25 °C): δ = 25.7 (CH ), 51.4 (NCH ), 114.0 (CH), 118.0
(CCl), 123.7 (CH), 128.2 (CH), 137.6 (CNO ), 150.6 (CNCH
2
), 6.65 (d, J = 9.1 Hz, 1 H, ArH), 7.97 (d, J =
1
3
1-Methyl-4-(4-nitrophenyl)piperazine: Table 2, Entry 3. Synthesized
CDCl
3
2
2
from 1-chloro-4-nitrobenzene (0.157 g, 1 mmol) and N-methylpip-
2
2
)
erazine (0.222 mL, 2 mmol). The product was isolated as a yellow
ppm. GC–MS: m/z = 225, 191, 179, 170, 154, 145, 117, 102, 89,
solid (0.121 g, 54%) after silica gel column chromatography (hex-
75.
1
ane/diethyl ether/acetone). H NMR (270 MHz, CDCl
3
, 25 °C): δ
1
-(2-Chloro-4-nitrophenyl)-4-methylpiperazine: Table 3, Entry 5.
Synthesized from 1,2-dichloro-4-nitrobenzene (0.192 g, 1 mmol)
and N-methylpiperazine (0.222 mL, 2 mmol). The product was iso-
=
5
(
(
2.35 (s, 3 H, CH
.1 Hz, 4 H, CH ), 6.82 (d, J = 9.4 Hz, 2 H, ArH) ppm. C NMR
67.8 MHz, CDCl , 25 °C): δ = 45.9 (NCH ), 46.8 (NCH ), 54.4
NCH ), 112.5 (CH), 125.8 (CH), 138.2 (CNO ), 154.7 (CNCH
3
), 2.55 (t, J = 5.1 Hz, 4 H, CH
2
), 3.43 (t, J =
1
3
2
3
3
2
lated as a yellow oil (0.194 g, 75%) after silica gel column
2
2
2
)
1
chromatography (hexane/dichloromethane/acetone).
270 MHz, CDCl , 25 °C): δ = 2.32 (s, 3 H, NCH
NCH ), 3.19 (s, 4 H, NCH ), 7.01 (d, J = 7.2 Hz, 1 H, ArH), 8.09
(dd, J = 10.0, 2.7 Hz, 1 H, ArH), 8.22 (d, J = 2.7 Hz, 1 H, ArH)
H NMR
ppm. GC–MS: m/z = 221, 179, 161, 150, 120, 104, 87, 70.
(
3
3
), 2.57 (s, 4 H,
1-Morpholino-4-nitrobenzene: Table 2, Entry 4. Synthesized from 1-
2
2
chloro-4-nitrobenzene (0.157 g, 1 mmol) and morpholine
1
3
(
(
0.175 mL, 2 mmol). The product was isolated as a yellow solid
ppm. C NMR (67.8 MHz, CDCl
(NCH ), 54.6 (NCH ), 119.2 (CH), 123.2 (CH), 126.4 (CH), 127.2
), 154.6 (CNCH ) ppm. GC–MS: m/z = 255,
213, 195, 184, 177, 154, 137, 102, 89, 71.
3 3
, 25 °C): δ = 45.9 (NCH ), 50.3
0.075 g, 36%) after alumina gel column chromatography (hexane/
2
2
1
diethyl ether). H NMR (270 MHz, CDCl
3
, 25 °C): δ = 3.37 (t, J (CCl), 141.8 (CNO
), 3.87 (t, J = 4.8 Hz, 4 H, CH ), 6.83 (d, J =
.1 Hz, 2 H, ArH), 8.13 (d, J = 9.7 Hz, 2 H, ArH) ppm. C NMR
67.8 MHz, CDCl , 25 °C): δ = 47.0 (NCH ), 66.3 (OCH ), 112.5
CH), 125.8 (CH), 138.8 (CNO ), 154.9 (CNCH ) ppm. GC–MS:
2
2
=
9
4.8 Hz, 4 H, CH
2
2
13
1
-(2-Bromo-4-nitrophenyl)-4-methylpiperazine: Table 3, Entry 6.
Synthesized from 2-bromo-1-chloro-4-nitrobenzene (0.236 g,
mmol) and N-methylpiperazine (0.222 mL, 2 mmol). The product
was isolated as a yellow oil (0.213 g, 71%) after silica gel column
(
(
3
2
2
2
2
1
m/z = 208, 192, 177, 161, 150, 120, 104, 77.
1
1-Nitro-4-pyrrolidinobenzene: Table 2, Entry 5. Synthesized from 1-
chromatography (hexane/diethyl ether/acetone).
(270 MHz, CDCl , 25 °C): δ = 2.38 (s, 3 H, NCH ), 2.63 (s, 4 H,
NCH ), 3.23 (s, 4 H, NCH ), 7.05 (d, J = 8.9 Hz, 1 H, ArH), 8.14
0.180 g, 93%) after silica gel column chromatography (hexane/ (dd, J = 6.4, 2.4 Hz, 1 H, ArH), 8.42 (d, J = 2.4 Hz, 1 H, ArH)
H
NMR
chloro-4-nitrobenzene (0.157 g, 1 mmol) and pyrrolidine
3
3
(
(
0.164 mL, 2 mmol). The product was isolated as a yellow solid
2
2
1
13
dichloromethane). H NMR (270 MHz, CDCl
3
, 25 °C): δ = 1.96
), 3.68 (t, J = 6.4 Hz, 4 H, NCH ), 6.31
d, J = 9.1 Hz, 2 H, ArH), 7.94 (d, J = 9.1 Hz, 2 H, ArH) ppm. (CH), 142.3 (CNO
ppm. C NMR (67.8 MHz, CDCl
(NCH ), 54.7 (NCH ), 117.4 (CBr), 119.6 (CH), 123.8 (CH), 129.7
), 156.2 (CNCH ) ppm. GC–MS: m/z = 301,
299, 257, 220, 192, 177, 149, 131, 119, 103, 89, 76, 71. MS (micrO-
TOF): calcd. for C11 14BrN 300.0342 and 302.0322; found
3 3
, 25 °C): δ = 45.9 (NCH ), 50.9
(
(
t, J = 6.4 Hz, 4 H, CH
2
2
2
2
2
2
13
C NMR (67.8 MHz, CDCl
3
, 25 °C): δ = 25.1 (CH
2
), 47.7
(
NCH ), 110.2 (CH), 126.0 (CH), 136.0 (CNO
2
2
), 151.6 (CNCH
2
)
H
3 2
O
Eur. J. Org. Chem. 2010, 6404–6408
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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