Transition Metal-Free Amination of Aryl Chlorides
J . Org. Chem., Vol. 66, No. 4, 2001 1411
5d was isolated as a light yellow liquid in 65% yield. 1H NMR
(360 MHz, 25 °C, CDCl3) δ ) 7.51-7.22 (m, 4H), 3.12-2.86
(m, 4H), 1.82 (br, 1H, NH), 1.66 (s, 9H); 13C{1H} NMR (90 MHz,
25 °C, CDCl3) δ ) 139.4, 132.1, 128.9, 129.0, 126.6, 124.6, 45.8,
44.6, 32.1, 29.7; MS (70 eV): m/z ) 211 (M+), 196, 153, 139,
125, 103, 86, 57.
Gen er a l P r oced u r e for th e Am in a tion of Ch lor oben -
zen es. In a pressure tube the aryl chloride (4.0 mmol) and
amine (2.0 mmol) were dissolved in 10 mL of toluene. After
addition of 3 equiv of KOt-Bu (6.0 mmol), the pressure tube
was sealed and heated to 135 °C. After 36 h, the reaction
mixture was allowed to cool to room temperature and was
quenched with 10 mL of water. The aqueous phase was
extracted three times with 10 mL of dichloromethane. The
combined organic phases were dried over magnesium sulfate,
and the solvent was removed in vacuo. The resulting crude
product was purified by column chromatography.
6.43 (d, J ) 8.4 Hz, 2H), 6.42 (s, 1H), 3.79 (t, J ) 4.8 Hz, 8H),
3.10 (t, J ) 4.8 Hz, 8H); 13C{1H} NMR (90 MHz, 25 °C, CDCl3)
δ ) 152.3, 129.7, 108.1, 103.9, 66.9, 49.6; MS (70 eV): m/z )
248 (M+), 233, 190, 132, 104, 77, 28.
N,N-Dip h en yla m in e (8g). Chlorobenzene (0.46 g, 4.0
mmol), aniline (0.18 mL, 2.0 mmol), and KOt-Bu (0.45 g, 4.0
mmol) were reacted according to the general procedure. After
column chromatography (hexane/ethyl acetate ) 10:1), 8g was
1
isolated as a liquid in 81% yield. H NMR (250 MHz, 25 °C,
CDCl3) δ ) 7.76-7.64 (m, 4H), 7.53 (d, J ) 8.4 Hz, 4H), 7.38
(t, J ) 8.4 Hz, 2H), 6.16 (br, 1H, NH); 13C{1H} NMR (63 MHz,
25 °C, CDCl3) δ ) 143.5, 129.8, 121.5, 118.4; MS (70 eV): m/z
) 169 (M+), 154, 139, 115.
Tr ip h en yla m in e (8h ). Chlorobenzene (0.69 g, 6.0 mmol),
aniline (0.18 mL, 2.0 mmol), and KOt-Bu (0.67 g, 6.0 mmol)
were reacted according to the general procedure. After column
chromatography (hexane/ethyl acetate ) 20:1), 8h was isolated
1
N-P h en ylp ip er id in e (8a ). Chlorobenzene (0.46 g, 4.0
mmol), piperidine (0.20 mL, 2.0 mmol), and KOt-Bu (0.67 g,
6.0 mmol) were reacted according to the general procedure.
After column chromatography (hexane/ethyl acetate ) 2:1), 8a
as a liquid in 78% yield. H NMR (250 MHz, 25 °C, CDCl3) δ
) 7.67 (t, J ) 7.5 Hz, 2H), 7.52 (d, J ) 7.5 Hz, 2H), 7.42 (t, J
) 7.5 Hz, 1H); 13C{1H} NMR (63 MHz, 25 °C, CDCl3) δ ) 148.3,
129.6, 124.6, 123.1; MS (70 eV): m/z ) 245 (M+), 167, 141,
115, 77, 51.
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was isolated as a liquid in 85% yield. H NMR (360 MHz, 25
°C, CDCl3) δ ) 7.20 (t, J ) 7.5 Hz, 2H), 6.88 (d, J ) 7.5 Hz,
2H), 6.78 (t, J ) 7.5 Hz, 1H), 3.13 (t, J ) 6.2 Hz, 4H), 1.69 (m,
4H), 1.53 (m, 2H); 13C{1H} NMR (90 MHz, 25 °C, CDCl3) δ )
152.0, 129.0, 121.1, 116.7, 51.0, 25.7, 24.2; MS (70 eV): m/z )
161 (M+), 132, 120, 105, 77, 51.
N-(3-Meth oxyp h en yl)a n ilin e (8i). 3-Chloroanisole (0.50
mL, 4.0 mmol), aniline (0.18 mL, 2.0 mmol), and KOt-Bu (0.67
g, 6.0 mmol) were reacted according to the general procedure.
After column chromatography (hexane/ethyl acetate ) 5:1), 8i
was isolated as a yellow liquid in 77% yield. 1H NMR (360
MHz, 25 °C, CDCl3) δ ) 7.56 (t, J ) 7.5 Hz, 2H), 7.39 (d, J )
7.5 Hz, 2H), 7.33 (t, J ) 7.5 Hz, 1H), 7.12 (t, J ) 7.5 Hz, 1H),
6.32-6.11 (m, 3H), 3.65 (s, 3H), 2.76 (s, 1H, NH); 13C{1H} NMR
(90 MHz, 25 °C, CDCl3) δ ) 161.1, 142.5, 139.4, 129.9, 129.5,
128.2, 117.8, 116.9, 110.3, 103.4, 55.2; MS (70 eV): m/z ) 199
(M+), 184, 170, 154, 129, 92, 51.
N,N-Di-n -bu tyla n ilin e (8b). Chlorobenzene (0.46 g, 4.0
mmol), di-n-butylamine (0.34 mL, 2.0 mmol), and KOt-Bu (0.67
g, 6.0 mmol) were reacted according to the general procedure.
After column chromatography (hexane/ethyl acetate ) 1:1), 8b
1
was isolated as a liquid in 72% yield. H NMR (360 MHz, 25
°C, CDCl3) δ ) 7.22 (t, J ) 7.7 Hz, 2H), 6.79 (d, J ) 7.7 Hz,
2H), 6.68 (t, J ) 7.7 Hz, 1H), 3.15 (t, J ) 7.9 Hz, 4H), 1.63 (m,
4H), 1.41 (m, 4H), 0.98 (t, J ) 7.8 Hz, 6H); 13C{1H} NMR (90
MHz, 25 °C, CDCl3) δ ) 147.2, 130.4, 119.2, 113.9, 49.5, 33.1,
20.8, 14.3; MS (70 eV): m/z ) 205 (M+), 162 (M+ - propyl),
120, 105, 77.
N-n -Bu tyl-(3-vin ylp h en yl)a m in e (8j). 2-Chlorostyrene
(0.25 mL, 2.0 mmol), n-butylamine (0.30 mL, 3.0 mmol), and
KOt-Bu (0.67 g, 6.0 mmol) were reacted according to the
general procedure. After column chromatography (hexane/
ethyl acetate ) 20:1), 8j was isolated as a yellow liquid in 52%
1
N,N-Diben zyla n ilin e (8c). Chlorobenzene (0.46 g, 4.0
mmol), dibenzylamine (0.39 mL, 2.0 mmol), and KOt-Bu (0.67
g, 6.0 mmol) were reacted according to the general procedure.
After column chromatography (hexane/ethyl acetate ) 20:1),
yield. H NMR (360 MHz, 25 °C, CDCl3) δ ) 7.14 (dd, J ) 7.9
Hz, J ) 7.5 Hz, 1H), 6.78 (d, J ) 7.5 Hz, 1H), 6.67 (dd, J )
10.9 Hz, J ) 17.6 Hz, 1H), 6.65 (dd, J ) 2.0 Hz, J ) 2.0 Hz,
1H), 6.53 (ddd, J ) 0.8 Hz, J ) 2.4 Hz, J ) 8.1 Hz, 1H), 5.72
(dd, J ) 17.6 Hz, J ) 1.2 Hz, 1H), 5.21 (dd, J ) 10.9 Hz, J )
1.0 Hz, 1H), 3.61 (s, 1H), 3.13 (t, J ) 7.1 Hz, 2H), 1.62 (m,
2H), 1.45 (m, 2H), 0.98 (t, J ) 7.3 Hz, 3H); 13C{1H} NMR (90
MHz, 25 °C, CDCl3) δ ) 148.7, 138.5, 137.4, 129.3, 115.4, 113.3,
112.4, 110.3, 43.6, 31.6, 20.3, 13.9; MS (70 eV): m/z ) 175
(M+), 132 (M+ - C3H7), 77.
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8c was isolated as a liquid in 76% yield. H NMR (400 MHz,
25 °C, CDCl3) δ ) 7.19 (m, 15H), 4.61 (s, 4H); 13C{1H} NMR
(100 MHz, 25 °C, CDCl3) δ ) 143.3, 138.6, 129.3, 128.7, 127.0,
126.8, 116.9, 112.6, 54.3; MS (70 eV): m/z ) 273 (M+), 196,
182, 91, 77, 65.
N-(1-Cycloh exyleth yl)-2,4-dim eth ylan ilin e (8d). 2-Chloro-
p-xylol (0.54 mL, 4.0 mmol), 1- cyclohexylethylamine (0.30 mL,
2.0 mmol), and KOt-Bu (0.67 g, 6.0 mmol) were reacted
according to the general procedure. After column chromatog-
raphy (hexane/ethyl acetate ) 20:1), 8d was isolated as a liquid
in 59% yield. 1H NMR (360 MHz, 25 °C, CDCl3) δ ) 7.37-
7.18 (m, 2H), 6.78 (s, 1H), 3.72 (s, 1H, NH), 2.71-2.44 (m, 7H),
2.41 (s, 3H), 2.08 (m, 3H), 1.66-1.38 (m, 8H); 13C{1H} NMR
(90 MHz, 25 °C, CDCl3) δ ) 145.5, 136.6, 130.5, 119.2, 117.9,
113.6, 43.0, 28.6, 28.5, 27.8, 26.5, 26.4, 21.6, 17.2; MS (70 eV):
m/z ) 231 (M+), 148, 132, 105, 41.
N-ter t-Bu tyl-(3-vin ylp h en yl)a m in e (8k ). 3-Chlorostyrene
(0.25 mL, 2.0 mmol), tert-butylamine (0.32 mL, 3.0 mmol), and
KOt-Bu (0.67 g, 6.0 mmol) were reacted according to the
general procedure. After column chromatography (hexane/
ethyl acetate ) 10:1), 8k was isolated as a light yellow liquid
1
in 26% yield. H NMR (360 MHz, 25 °C, CDCl3) δ ) 7.13 (dd,
J ) 7.7 Hz, J ) 7.9 Hz, 1H), 6.85 (d, J ) 7.7 Hz, 1H), 6.79 (dd,
J ) 2.0 Hz, J ) 1.8 Hz, 1H), 6.70-6.62 (m, 2H), 5.70 (dd, J )
17.6 Hz, J ) 1.2 Hz, 1H), 5.21 (dd, J ) 10.9 Hz, J ) 1.0 Hz,
1H), 3.41 (s, 1H), 1.36 (s, 9H); 13C{1H} NMR (90 MHz, 25 °C,
CDCl3) δ ) 147.0, 138.2, 137.3, 129.0, 117.0, 116.4, 115.3,
113.2, 51.5, 30.1; MS (70 eV): m/z ) 175 (M+), 160, 119, 77,
41.
N-(3-Ch lor op h en yl)m or p h olin e (8e). 1,3-Dichloroben-
zene (0.23 mL, 2.0 mmol), morpholine (0.45 mL, 5.0 mmol),
and KOt-Bu (0.67 g, 6.0 mmol) were reacted according to the
general procedure. After column chromatography (hexane/
ethyl acetate ) 1:1), 8e was isolated as a light yellow liquid
N,N-Dim eth yl-3-m eth oxya n ilin e (8l). 3-Chloroanisole
(0.50 mL, 4.0 mmol), diethylamine (0.29 g, 4.0 mmol), and KOt-
Bu (0.67 g, 6.0 mmol) were reacted according to the general
procedure. After column chromatography (hexane/ethyl acetate
) 5:1), 8l was isolated as a yellow liquid in 93% yield. 1H NMR
(360 MHz, 25 °C, CDCl3) δ ) 7.10 (dd, J ) 7.5 Hz, J ) 8.4 Hz,
1H), 6.30-6.19 (m, 3H), 3.76 (s, 3H), 3.30 (q, J ) 7.1 Hz, 4H),
1.14 (t, J ) 7.1 Hz, 6H); 13C{1H} NMR (90 MHz, 25 °C,
CDCl3): δ ) 161.0, 149.2, 129.9, 105.2, 100.1, 98.5, 55.0, 44.4,
12.6; MS (70 eV): m/z ) 179 (M+), 164, 150, 136, 108, 77.
Bis-1,3-piper idin oben zen e (8m ). 1,3-Dichlorobenzene (0.23
mL, 2.0 mmol), piperidine (0,51 g, 6.0 mmol), and KOt-Bu (0.90
g, 8.0 mmol) were reacted according to the general procedure.
After column chromatography (hexane/ethyl acetate ) 2:1), 8m
1
in 68% yield. H NMR (360 MHz, 25 °C, CDCl3) δ ) 7.14 (t, J
) 8.0 Hz, 1H), 6.87 (s, 1H), 6.81 (d, J ) 8.0 Hz, 1H), 6,74 (d,
J ) 8.0 Hz, 1H), 3.82 (t, J ) 4.9 Hz, 4H), 3.11 (t, J ) 4.9 Hz,
4H); 13C{1H} NMR (90 MHz, 25 °C, CDCl3) δ ) 152.2, 135.0,
130.4, 119.7, 115.5, 113.6, 66.6, 28.9; MS (70 eV): m/z ) 197
(M+), 139, 111, 75.
1,3-Bism or ph olin oben zen e (8f). 1,3-Dichlorobenzene (0.23
mL, 2.0 mmol), morpholine (0.72 mL, 8.0 mmol), and KOt-Bu
(0.90 g, 8.0 mmol) were reacted according to the general
procedure. After column chromatography with (hexane/ethyl
acetate ) 2:1), 8f was isolated as a liquid in 78% yield. 1H
NMR (360 MHz, 25 °C, CDCl3) δ ) 7.14 (t, J ) 8.4 Hz, 1H),