Pd-Catalyzed Aryl Amination
FULL PAPER
29.7 ppm (À); elemental analysis calcd (%) for C16H20NBr: C 62.75, H
Et2O in pentane) as a light yellow oil. The spectral data were in accord-
ance with those reported in literature.[38]
6.58, N 4.57; found: C 62.61, H 6.79, N 4.65.
N-Methyl-N-phenyl-3-aminothiophene (20) (Table 2): Following general
procedure A (1 mL of toluene at 1008C instead of DME at 808C),
138 mg of 20 (73% yield) were isolated (Rf =0.2, step gradient, 5% Et2O
in pentane followed by 25% Et2O in pentane) as a yellow oil. The spec-
tral data were in accordance with those reported in literature.[36]
N-(2,6-Dimethylphenyl)2,6-diisopropylaniline (30) (Table 3): Following
general procedure A (RT), 253mg of 30 (90% yield) were isolated (Rf =
0.3, 5% Et2O in pentane) as a colorless oil. The spectral data were in ac-
cordance with those reported in literature.[33]
1-(6-Methoxypyridin-2-yl)-4-methylpiperazine (31) (Table 3): Following
general procedure A (RT), the crude residue was taken up in Et2O
(100 mL) and washed with 1m HCl (250 mL). The organic layer was
discarded and the combined aqueous layers were adjusted to pH ꢀ10
using a solution of 10m KOH. The aqueous layer was extracted with
Et2O (3100 mL), dried over anhydrous MgSO4, filtered and concentrat-
ed in vacuo. Following this, 205 mg of 31 (99% yield) were isolated (Rf =
0.50, 10% methanol in dichloromethane) as a light yellow, viscous oil.
1H NMR (300 MHz, CDCl3): d = 7.39 (t, J=8.1 Hz, 1H), 6.15 (d, J=
7.8 Hz, 1H), 6.08 (d, J=8.1 Hz, 1H), 3.87 (s, 3H), 3.54 (t, J=5.1 Hz,
4H), 2.51 (t, J=5.1 Hz, 4H), 2.34 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3) APT: d 163.1 (+), 158.3( +), 140.1 (À), 98.2 (À), 98.1 (À), 54.9
(+), 52.9 (À), 46.2 (À), 45.2 ppm (+); elemental analysis calcd (%) for
C11H17N3O: C 63.74, H 8.27, N 20.27; found: C 63.42, H 8.42, N 20.67.
N-Benzyl-N-isopropyl-3,4,5-trimethoxyaniline (21) (Table 2): Following
general procedure A (508C), 176 mg of 21 (58% yield) were isolated
(Rf =0.30, 20% Et2O in pentane) as
a
clear, viscous oil. 1H NMR
(400 MHz, CDCl3): d = 7.40–7.20 (m, 5H), 5.98 (s, 2H), 4.40 (s, 2H),
4.22 (quin., J=6.4 Hz, 1H), 3.79 (s, 3H), 3.74 (s, 6H), 1.27 ppm (d, J=
6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) APT: d = 153.6 (+), 146.2
(+), 140.9 (+), 129.8 (+), 128.5 (À), 126.5 (À), 126.3( À), 92.0 (À), 61.0
(À), 55.9 (À), 49.0 (À), 48.9 (+), 20.0 ppm (À); elemental analysis calcd
(%) for C19H25NO3: C 72.35, H 7.99, N 4.44; found: C 72.01, H 8.24, N
4.66.
N,N-Bis(2-ethylhexyl)-6-methoxy-2-aminopyridine (22) (Table 2): Follow-
ing general procedure A (508C), 261 mg of 22 (75% yield) were isolated
(Rf =0.25, pentane) as a light yellow, viscous oil. 1H NMR (400 MHz,
CDCl3): d = 7.32 (t, J=8.0 Hz, 1H), 5.97 (d, J=8.0 Hz, 1H), 5.92 (d, J=
8.0 Hz, 1H), 3.89 (s, 3H), 3.42–3.32 (m, 4H), 1.90–1.78 (m, 2H), 1.48–
1.21 (m, 16H), 0.95–0.85 ppm (m, 12H); 13C NMR (75 MHz, CDCl3)
APT: d = 162.9 (+), 157.3( +), 139.3 (À), 97.2 (À), 95.0 (À), 53.5 (+),
52.8 (À), 37.4 (À), 30.7 (+), 28.8 (+), 24.0 (+), 23.2 (+), 14.1 (À),
10.8 ppm (À); elemental analysis calcd (%) for C22H40N2O: C 75.81, H
11.57, N 8.04; found: C 75.71, H 11.84, N 8.47.
1-Formyl-4-(4-(trifluoromethyl)phenyl)piperazine (32) (Table 3): Follow-
ing general procedure A (RT), 153mg of 32 (59% yield) were isolated
(Rf =0.25, ethyl acetate) as
a
white solid (m.p. 70–738C). 1H NMR
(400 MHz, CDCl3): d = 8.15 (s, 1H), 7.53(d, J=8.4 Hz, 2H), 6.97 (d, J=
8.4 Hz, 2H), 3.74 (t, J=4.8 Hz, 2H), 3.57 (t, J=4.8 Hz, 2H), 3.32 (t, J=
5.2 Hz, 2H), 3.28 ppm (t, J=5.2 Hz, 2H); 13C NMR (75 MHz, CDCl3)
APT: d = 160.7 (À), 153.0 (+), 126.5 ((À), q, J=3.8 Hz), 124.6 ((+), q,
J=269 Hz), 121.5 ((+), q, J=33 Hz), 115.3 (À), 49.2 (+), 48.0 (+),
45.1 ppm (+), 39.6 ppm (+); elemental analysis calcd (%) for
C12H13F3N2O: C 55.81, H 5.07, N 10.85; found: C 56.14, H 5.36, N 10.77.
3,4,5-Trimethoxy-N,N-bis(2-methoxyethyl)aniline (23) (Table 2): Follow-
ing general procedure A (508C), the crude residue was taken up in Et2O
(100 mL) and washed with 1m HCl (350 mL). The organic layer was
discarded and the combined aqueous layers were adjusted to pH ꢀ10
using a solution of 10m KOH. The aqueous layer was extracted with
Et2O (3100 mL), dried over anhydrous MgSO4, filtered and concentrat-
ed in vacuo. Following this, 213mg of 23 (71% yield) were isolated (Rf =
0.60, step gradient, 60% Et2O in pentane followed by 80% Et2O in pen-
tane) as a clear, viscous oil. 1H NMR (400 MHz, CDCl3): d = 6.00 (s,
2H), 3.85 (s, 6H), 3.78 (s, 3H), 3.60–3.48 (m, 8H), 3.38 ppm (s, 6H);
13C NMR (100 MHz, CDCl3) APT: d = 153.8 (+), 145.0 (+), 129.8 (+),
90.6 (À), 70.5 (+), 61.1 (À), 59.0 (À), 56.1 (À), 51.5 ppm (+); elemental
analysis calcd (%) for C15H25NO5: C 60.18, H 8.42, N 4.68; found: C
59.92, H 8.60, N 4.97.
(S)-2,6-Dimethyl-N-(1-phenylethyl)aniline (33) (Table 3): Following gen-
eral procedure A (RT), 176 mg of 33 (78% yield) were isolated (Rf =0.4;
5% Et2O in pentane) as a yellow, viscous oil. Following general proce-
dure B, 221 mg of 33 (98%) were isolated. [a]2D0 = À100.88 (c=0.73,
CHCl3); 1H NMR (400 MHz, CDCl3): d = 7.45–7.25 (m, 5H), 7.05 (d,
J=7.5 Hz, 2H), 6.88 (t, J=7.5 Hz, 1H), 4.41 (q, J=6.8 Hz, 1H), 3.24 (br.
s, 1H), 2.26 (s, 6H), 1.60 ppm (d, J=6.8 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d: 145.4 (+), 145.0 (+), 130.5 (+), 128.9 (À), 128.5 (À), 127.0
(À), 126.2 (À), 121.7 (À), 56.8 (À), 22.7 (À), 19.0 ppm (À); elemental
analysis calcd (%) for C16H19N: C 85.28, H 8.50, N 6.22; found: C 84.97,
H 8.26, N 5.90.
1-Methyl-4-(pyridin-2-yl)piperazine (24) (Table 2): Following general pro-
cedure A (508C, completed using 150 mmol of aryl chloride), the crude
material was taken up in Et2O (1 L) and washed with 1m HCl (2
500 mL). The organic layer was discarded and the combined aqueous
layers were adjusted to pH ꢀ10 using a solution of 10m KOH. The aque-
ous layer was extracted with Et2O (3500 mL), dried over anhydrous
MgSO4, filtered and concentrated in vacuo. Following this, 26.1 g of 24
(98% yield) were isolated as a light yellow, viscous oil. The spectral data
were in accordance with those reported in literature.[37]
N,4-Dimethyl-N-phenylquinolin-2-amine (34) (Table 5): Following gener-
al procedure B, 201 mg of 34 (81% yield) were isolated (Rf =0.15, 3%
Et2O in pentane) as colorless, viscous oil. H NMR (300 MHz, CDCl3): d
= 7.90–7.75 (m, 2H), 7.60 (dt, J=7.5, 1.5 Hz, 1H), 7.50–7.40 (m, 2H),
7.38–7.25 (m, 4H), 6.64 (s, 1H), 3.66 (s, 3H), 2.48 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3) APT: d 157.0 (+), 148.0 (+), 146.7 (+), 144.0 (+),
129.8 (À), 129.2 (À), 127.2 (À), 126.7 (À), 125.8 (À), 123.8 (+), 123.5 (À),
122.3( À), 112.2 (À), 38.6 (À), 18.9 ppm (À); elemental analysis calcd
(%) for C17H16N2: C 82.22, H 6.49, N 11.28; found: C 81.97, H 6.79, N
11.37.
1
N-Methyldiphenylamine (25) (Table 3): Following general procedure A
(RT), 139 mg of 25 (76% yield) were isolated (Rf =0.3, 5% Et2O in pen-
tane) as a white, crystalline solid. The spectral data were in accordance
with those reported in literature.[33]
4-(Pyrazin-2-yl)morpholine (35) (Table 5): Following general procedure
B, 142 mg of 35 (86% yield) were isolated (Rf =0.4, Et2O) as an off-
1
white solid (m.p. 46–488C). H NMR (300 MHz, CDCl3): d = 8.14 (d, J=
2,4,6-Trimethyl-N-phenylaniline (26) (Table 3): Following general proce-
dure A (RT), 141 mg of 26 (67% yield) were isolated (Rf =0.3, 5% Et2O
in pentane) as a colorless oil.[33]
1.5 Hz, 1H), 8.10–8.04 (m, 1H), 7.91 (d, J=2.4 Hz, 1H), 3.84 (t, J=
2.4 Hz, 4H), 3.58 ppm (t, J=2.4 Hz, 4H); 13C NMR (75 MHz, CDCl3)
APT: d = 155.1 (+), 141.8 (À), 133.6 (À), 130.9 (À), 66.5 (+), 44.8 ppm
(+); elemental analysis calcd (%) for C8H11N3O2: C 58.17, H 6.71, N
25.44; found: C 58.18, H 6.90, N 25.27.
2-Piperidinylpyridine (27) (Table 3): Following general procedure
A
(RT), 135 mg of 27 (83% yield) were isolated (Rf =0.3, 10% Et2O in
pentane) as a colorless oil. The spectral data were in accordance with
those reported in literature.[20g]
6-Methoxy-N-methyl-N-phenyl-2-aminopyridine (36) (Table 5): Following
general procedure B, 201 mg of 36 (94% yield) were isolated (Rf =0.2,
step gradient, pentane followed by 2% Et2O in pentane) as an off-white
4-(Pyridin-2-yl)morpholine (28) (Table 3): Following general procedure
A (RT), 142 mg of 28 (87% yield) were isolated (Rf =0.35, 50% Et2O in
pentane) as a yellow oil. The spectral data were in accordance with those
reported in literature.[20f]
solid (m.p. 44–458C). 1H NMR (400 MHz, CDCl3): d
= 7.43(t, J=
8.0 Hz, 2H), 7.35–7.20 (m, 4H), 6.12 (d, J=4.0 Hz, 1H), 6.10 (d, J=
3.6 Hz, 1H), 3.95 (s, 3H), 3.53 ppm (s, 3H); 13C NMR (100 MHz, CDCl3)
APT: d 163.2 (+), 157.6 (+), 146.8 (+), 139.4 (À), 129.4 (À), 126.3( À),
125.2 (À), 100.1 (À), 97.3( À), 53.1 (À), 38.1 ppm (À); elemental analysis
1-(4-Methoxyphenyl)pyrrolidine (29) (Table 3): Following general proce-
dure A (RT), 107 mg of 29 (60% yield) were isolated (Rf =0.4, 10%
Chem. Eur. J. 2008, 14, 2443– 2452
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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