The Journal of Organic Chemistry
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with hexane−AcOEt (90:10 v/v) as the eluent to give the 4-
phenylmorpholine (3a, 47.1 mg, 93%) as a white solid. The recovered
second generation SAPd catalyst was again subjected to the above
reaction condition for a second cycle, and this procedure was repeated
for a total of 10 cycles.
Colorless oil: H NMR (400 MHz, CDCl3) δ 7.22−7.17 (2H, m),
6.65−6.60 (3H, m), 3.25 (4H, t, J = 7.4 Hz), 1.60−1.52 (4H, m),
1.40−1.30 (4H, m), 0.95 (6H, t, J = 7.3 Hz); 13C NMR (100 MHz,
CDCl3) δ 148.1, 129.1, 115.0, 111.6, 50.7, 29.3, 20.3, 14.0; LRMS (EI)
m/z 205 (70%, M+).
N-Methyl-N-phenylaniline (3e).14
Typical Experimental Procedure of Buchwald−Hartwig
Coupling Reaction Using Chlorobenzene Catalyzed by the
Second Generation SAPd, Table 5, Entry 1. A mixture of
chlorobenzene (4, 50.0 mg, 0.44 mmol), morpholine (2a, 46.0 mg,
0.53 mmol), and KOt-Bu (69.0 mg, 0.62 mmol) in xylene (1.0 mL)
was heated in the presence of second generation SAPd in a glovebox
for 12 h at 130 °C. The reaction mixture was cooled to room
temperature, and the second generation SAPd (immobilized Pd: 57
16 μg = 0.12 mol %) was recovered from the cold reaction mixture and
washed several times with xylene. The reaction mixture was poured
into water (5.0 mL), and the organic layer was extracted with AcOEt
(3 × 10 mL). The combined organic extracts were washed with brine
(3 × 10 mL) and dried over Na2SO4. Concentration at reduced
pressure gave a yellowish oil, which was chromatographed on silica gel
with hexane−AcOEt (90:10 v/v) as the eluent to give the 4-
phenylmorpholine (3a, 63.8 mg, 88%) as a white solid. The recovered
second generation SAPd catalyst was again subjected to the above
reaction condition for a second cycle, and this procedure was repeated
for a total of 10 cycles.
By following the same procedure described for 3a, amine 3e was
prepared from bromobenzene (1a) and N-methylaniline (2e). Average
yield: 92%.
Yellowish oil: 1H NMR (400 MHz, CDCl3) δ 7.27 (4H, dd, J = 7.8
and 7.8 Hz), 7.02 (4H, d, J = 7.8 Hz), 6.95 (2H, d, J = 7.3 Hz), 3.32
(3H, s); 13C NMR (100 MHz, CDCl3) δ 148.9, 129.1, 121.2, 120.3,
40.1; LRMS (EI) m/z 183 (100%, M+).
N-Benzylaniline (3f).15
By following the same procedure described for 3a, amine 3f was
prepared from bromobenzene (1a) and benzylamine (2f). Average
yield: 88%.
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Yellowish oil: H NMR (500 MHz, CDCl3) δ 7.38−7.32 (4H, m),
7.26 (1H, dd, J = 7.5 and 7.5 Hz), 7.19−7.15 (2H, m), 6.71 (1H, dd, J
= 7.3 and 7.3 Hz), 6.63 (2H, d, J = 6.4 Hz), 4.32 (2H, s), 4.02 (1H,
brs); 13C NMR (125 MHz, CDCl3) δ 148.1, 139.4, 129.2, 128.6, 127.4,
127.1, 117.5, 112.7, 48.2; LRMS (EI) m/z 183 (100%, M+).
N-Cyclohexylaniline (3g).16
4-Phenylmorpholine (3a).10,11
From arylbromide method. Average yield: 92%.
From arylchloride method. Average yield: 88%.
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White solid: H NMR (400 MHz, CDCl3) δ 7.28−7.23 (2H, m),
6.90−6.85 (3H, m), 3.82 (4H, t, J = 4.6 Hz), 3.11 (4H, t, J = 4.6 Hz);
13C NMR (100 MHz, CDCl3) δ 151.1, 129.0, 119.8, 115.5, 66.7, 49.1;
LRMS (EI) m/z 163 (100%, M+).
By following the same procedure described for 3a, amine 3g was
prepared from bromobenzene (1a) and cyclohexylamine (2g).
Average yield: 91%.
Yellowish oil: 1H NMR (500 MHz, CDCl3) δ 7.15 (2H, dd, J = 7.8
and 7.8 Hz), 7.65 (1H, dd, J = 7.8 and 7.8 Hz), 6.59 (2H, d, J = 7.3
Hz), 3.51 (1H, br s), 3.27−3.23 (1H, m), 2.07−2.05 (2H, m), 1.78−
1.74 (2H, m), 1.67−1.64 (1H, m), 1.41−1.32 (2H, m), 1.26−1.11(3H,
m); 13C NMR (125 MHz, CDCl3) δ 147.3, 129.1, 116.7, 113.0, 51.5,
33.3, 25.8, 24.9; LRMS (EI) m/z 175 (50%, M+).
8-Phenyl-1,4-dioxa-8-azaspiro[4.5]decane (3b).12
From arylbromide method: By following the same procedure
described for 3a, amine 3b was prepared from bromobenzene (1a)
and 1,4-dioxa-8-azaspiro[4.5]decane (2b). Average yield: 91%.
From arylchloride method: By following the same procedure
described for 3a, amine 3b was prepared from chlorobenzene (1h) and
1,4-dioxa-8-azaspiro[4.5]decane (2b). Average yield: 92%.
4-(4-Methoxyphenyl)morpholine (3h).17
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By following the same procedure described for 3a, amine 3h was
prepared from 4-bromoanisole (1b) and morpholine (2a). Average
yield: 92%.
Yellowish oil: H NMR (400 MHz, CDCl3) δ 7.25−7.20 (2H, m),
6.9 (2H, d, J = 8.7 Hz), 6.83−6.79 (1H, dd, J = 7.4 and 7.4 Hz), 3.9
(4H, s), 3.80 (4H, t, J = 5.5 Hz), 1.82 (4H, t, J = 5.5 Hz); 13C NMR
(100 MHz, CDCl3) δ 150.8, 128.9, 119.3, 116.4, 107.0, 64.1, 47.6,
34.4; LRMS (EI) m/z 219 (55%, M+).
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White solid: H NMR (500 MHz, CDCl3) δ 6.90−6.84 (4H, m),
3.86 (4H, t, J = 4.8 Hz), 3.77 (3H, s), 3.05 (4H, t, J = 4.8 Hz); 13C
NMR (125 MHz, CDCl3) δ 153.9, 145.6, 117.8, 114.4, 67.0, 55.5,
50.8; LRMS (EI) m/z 193 (60%, M+).
1-Phenylpiperidine (3c).13
4-Morpholinobenzonitrile (3i).17
By following the same procedure described for 3a, amine 3c was
prepared from bromobenzene (1a) and piperidine (2c). Average yield:
96%.
By following the same procedure described for 3a, amine 3i was
prepared from 4-bromobenzonitrile (1c) and morpholine (2a).
Average yield: 88%.
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Colorless oil: H NMR (400 MHz, CDCl3) δ 7.27−7.23 (2H, m),
6.94 (2H, d, J = 7.8 Hz), 6.82 (1H, dd, J = 7.3 and 7.3 Hz), 3.15 (4H,
t, J = 5.0 Hz), 1.74−1.68 (4H, m), 1.60−1.54 (2H, m); 13C NMR (100
MHz, CDCl3) δ 152.1, 128.9, 119.1, 116.4, 50.5, 25.8, 24.2; LRMS
(EI) m/z 116 (100%, M+).
Yellowish solid: 1H NMR (500 MHz, CDCl3) δ 7.52 (2H, d, J = 8.7
Hz), 6.87 (2H, d, J = 8.6 Hz), 3.85 (4H, t, J = 4.6 Hz), 3.28 (4H, t, J =
4.6 Hz); 13C NMR (125 MHz, CDCl3) δ 153.4, 133.4, 119.8, 114.0,
100.8, 66.4, 47.2; LRMS (EI) m/z 188 (60%, M+).
N,N-Dibutylaniline (3d).13
4-(Naphthalen-2-yl)morpholine (3j).18
By following the same procedure described for 3a, amine 3d was
prepared from bromobenzene (1a) and n-dibutylamine (2d). Average
yield: 97%.
By following the same procedure described for 3a, amine 3j was
prepared from 2-bromonaphthalene (1d) and morpholine (2a).
Average yield: 91%.
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dx.doi.org/10.1021/jo4011415 | J. Org. Chem. 2013, 78, 7575−7581