Examination of the Aromatic Amination Catalyzed by Palladium on Charcoal
Phos (1.8 mg, 0.005 mmol), NaO-t-Bu (96.7 mg, 0.75 mmol),
tert-butyl alcohol (250 mL) , aryl iodide (0.5 mmol) and
amine (0.75 mmol) were added into the vial. The reaction
mixture was heated to 808C, and the reaction was followed
by GC. After the consumption of the aryl iodide (2–4 h) the
mixture was cooled to room temperature. After the removal
of the catalyst the solvent was evaporated and the crude
product was purified by column chromatography using hexa-
ne:EtOAc and dichloromethane:MeOH as eluent.
(% relative intensity, ion)=253 (50, [M+]), 238 (100), 167
(25); HR-MS (ESI): m/z=254.1180, calculated for
C16H16NO2 [M+H]+: 254.1176.
2-Isopropyl-N-ACTHNUTRGNEUNG(p-tolyl)benzeneamine (3n): Pale yellow
oil; yield: 82 mg (0.37 mmol, 73%); Rf (DCM:MeOH
10:1)=0.75; 1H NMR (CDCl3; 250 MHz): d=7.19 (d, 2H,
J=7.42 Hz), 7.11–6.90 (m, 4H), 6.75 (d, 2H, J=7.90 Hz),
5.27 (bs, 1H), 3.10–2.98 (m, 1H), 2.20 (s, 3H), 1.18 (s, 3H),
1.15 (s,3H); 13C NMR (CDCl3, 62.5 MHz): d 142.3, 140.3,
139.2, 129.8, 129.6, 126.4, 122.9, 122.5, 120.3, 117.5, 27.6,
22.9, 20.6; MS (EI, 70 eV): m/z (% relative intensity, ion)=
225 (80, [M+]), 210 (75), 194 (50), 180 (100), 167 (15), 118
(15), 96 (20); HR-MS (ESI): m/z=226.1591, calculated for
C16H20N [M+H]+: 226.1590.
1-Methyl-4-(m-tolyl)piperazine (3p): Colourless oil; yield:
76 mg (0.40 mmol, 80%); Rf (hexane:EtOAc 10:1)=0.43;
1H NMR (CDCl3; 250 MHz): d=7.20–7.13 (m, 1H), 6.78–
6.68 (m, 3H), 3.24–3.20 (m, 4H), 2.60–2.56 (m, 4H), 2.36
(s,3H), 2.34 (s, 3H); 13C NMR (CDCl3, 62.5 MHz): d=
151.2, 138.6, 128.8, 120.5, 116.8, 113.1, 55.1, 49.0, 46.0, 21.7;
IR: n=3039, 2936, 2793, 2284, 1601, 1583, 1493, 1451, 1376,
1338, 1292, 1246, 1187, 1142, 1006, 954, 839 cmÀ1; MS (EI,
70 eV): m/z (% relative intensity, ion)=190 (100, [M+]), 175
(15), 146 (15), 119 (90), 105 (15), 91 (55), 71 (60); HRMS
(ESI): m/z=191.1542, calculated for C12H19N2 [M+H]+:
291.1543.
General Procedure for the Coupling of Aryl
Bromides
A 4-mL screw-capped vial was charged with argon. 10%
Pd/C, Selcat Q6 (5.3 mg, 0.005 mmol), DicyclohexylJohn-
Phos (1.8 mg, 0.005 mmol), NaO-t-Bu (96.7 mg, 0.75 mmol),
tert-butyl alcohol (250 mL), aryl bromide (0.5 mmol) and
amine (0.75 mmol) were added into the vial, which was
purged with argon once again. The reaction mixture was
heated to 1008C, and the reaction was followed by GC.
After the consumption of the aryl bromide (6–8 h) the mix-
ture was cooled to room temperature. After the removal of
the catalyst the solvent was evaporated and the crude prod-
uct was purified by column chromatography using hexa-
ne:EtOAc and dichloromethane (DCM):MeOH as eluent.
1-Methyl-4-(naphthalen-6-yl)piperazine (3r): Colourless
crystals; yield: 101 mg (0.45 mmol, 89%); mp 74–768C; Rf
(hexane:EtOAc 10:1)=0.39; 1H NMR (CDCl3; 250 MHz):
d=7.65–7.61 (m, 3H), 7.34–7.07 (m, 4H), 3.25–3.24 (m, 4H),
2.57–2.55 (m, 4H), 2.30 (s, 3H); 13C NMR (CDCl3,
62.5 MHz): d=149.0, 134.5, 128.6, 127.3, 126.7, 126.2, 123.3,
119.3, 110.2, 55.1, 49.4, 46.1; MS (EI, 70 eV): m/z (% rela-
tive intensity, ion)=226 (25, [M+]), 173 (100), 145 (35); IR:
n=2943, 2803, 1622, 1595, 1507, 1449, 1379, 1290, 1257,
1220, 1144, 1006, 959, 82588cmÀ1; HR-MS (ESI): m/z=
227.1546, calculated for C15H19N2 [M+H]+: 227.1543.
1-Methyl-4-(pyridin-2-yl)piperazine (3u): Colourless oil;
yield: 64 mg (0.36 mmol, 72%); Rf (hexane: EtOAc=
General Procedure for the Coupling of Aryl
Chlorides
A 4-mL screw-capped vial was charged with argon. 10%
Pd/C, Selcat Q6 (10.6 mg, 0.01 mmol), DicyclohexylJohn-
Phos (3.6 mg, 0.01 mmol), NaO-t-Bu (96.7 mg, 0.75 mmol),
2-methyl-2-butanol (250 mL), aryl chloride (0.5 mmol) and
amine (0.75 mmol) were added into the vial, which was
purged with argon once again. The reaction mixture was
heated to 1108C, and the reaction was followed by GC.
After the consumption of the aryl chloride (6–8 h) the mix-
ture was cooled to room temperature. After the removal of
the catalyst the solvent was evaporated and the crude prod-
uct was purified by column chromatography using hex-
1
10:1)=0.38; H NMR (CDCl3; 250 MHz): d=8.16–8.13 (m,
1H), 7.47–7.39 (m, 1H), 6.62–6.55 (m, 2H), 3.54–3.50 (m,
4H), 2.51–2.46 (m, 4H), 2.30 (s, 3H); 13C NMR (CDCl3,
62.5 MHz): d=159.4, 147.8, 137.83 113.2, 107.0, 54.8, 46.1,
45.0; MS (EI, 70 eV): m/z (% relative intensity, ion)=177
(20, [M+]), 133 (20), 120 (20), 107 (100), 79 (30), 71 (20);
HR-MS (ESI): m/z=178.1345, calculated for C10H16N3 [M+
H]+: 178.1339.
N-(4-Methoxyphenyl)pyridin-2-amine (3v): Brown crys-
tals, X=Cl yield: 74 mg (0.37 mmol, 73%); Rf (hexane)=
0.68; mp 62–648C 1H NMR (CDCl3; 250 MHz): d=8.07–
8.04 (m, 1H), 7.37–7.30 (m, 1H), 7.14 (d, 2H, J=9.00 Hz),
6.79–6.78 (m, 3H), 6.61–6.54 (m, 2H), 3.72 (s, 3H);
13C NMR (CDCl3, 62.5 MHz): d=157.4, 156.2, 148.3, 137.6,
133.3, 124.0, 114.5, 114.1, 107.1, 55.5; MS (EI, 70 eV): m/z
(% relative intensity, ion)=200 (95, [M+]), 199 (75), 185
(100), 156 (30), 78 (55); HR-MS (ESI): m/z=201.1025, cal-
culated for C12H13N2O [M+H]+: 201.1022.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
oil; yield: 101 mg (0.42 mmol, 83%); Rf (DCM:MeOH
10:1)=0.66; 1H NMR (CDCl3; 250 MHz): d=7.06 (d, 2H,
J=8.21 Hz), 6.90 (d, 2H, J=8.53 Hz), 6.80 (d, 1H, J=
8.53 Hz), 6.66 (d, 1H, J=2.37 Hz), 6.60 (dd, 1H, J1 =
8.53 Hz, J2 =2.53 Hz), 5.49 (bs, 1H), 3.86 (s, 3H), 3.82 (s,
3H) 2.30 (s, 3H); 13C NMR (CDCl3, 62.5 MHz): d=150.0,
144.5, 142.4, 137.6, 130.3, 130.0, 130.0, 117.4, 112.7, 111.3,
104.7, 56.7, 56.2, 21.0; IR: n=3368, 3130, 1609, 1545, 1505,
1350, 1303, 1256, 1225, 1197, 1160, 1132, 1023 cmÀ1; MS (EI,
70 eV): m/z (% relative intensity, ion)=243 (100, [M+]), 228
(100), 200 (20), 155 (15); HR-MS (ESI): m/z=245.1367, cal-
culated for C15H18NO2 [M+H]+: 245.1365.
Di-(4-acetylphenyl)amine (3m): Yellow crystals; X=I
yield: 122 mg (0.48 mmol, 96%); X=Cl yield: 96 mg
(0.38 mmol, 76%); mp: 117–1198C; Rf (hexane : EtOAc=
10:1)=0.35; 1H NMR (CDCl3; 250 MHz): d=7.91 (d, 4H,
J=8.85 Hz), 7.16 (d, 4H, J=8.85 Hz), 6.83 (bs, 1H), 2.56
(s,6H); 13C NMR (CDCl3, 62.5 MHz): d 196.6, 146.0, 130.4,
116.9, 113.6, 26.3; IR: n=3307, 1677, 1655, 1580, 1524, 1427,
1338, 1269, 1249, 1171, 954, 823 cmÀ1; MS (EI, 70 eV): m/z
Adv. Synth. Catal. 2010, 352, 1523 – 1532
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1531