Page 9 of 14
The Journal of Organic Chemistry
(neat, cm-1): 3383, 1587, 1494, 742, 688. Anal. Calcd. For
– 7.14 (m, 2H), 6.70 (dddd, J = 7.3, 7.3, 1.1, 1.1 Hz, 1H), 6.64
1
2
3
4
5
6
7
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– 6.59 (m, 2H), 3.65 (t, J = 6.5 Hz, 2H), 3.12 (t, J = 7.1 Hz,
2H), 1.68 – 1.54 (m, 4H), 1.48 – 1.38 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3) δ 148.6, 129.3, 117.3, 112.9, 63.0, 44.0,
32.8, 29.7, 27.1, 25.7. IR (neat, cm-1): 3553, 2928, 2856, 1601,
1505, 747, 691. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C12H20NO 194.1539; Found: 194.1530.
C12H11N: C, 85.17; H, 6.55. Found: C, 84.91; H, 6.54.
1-(4-(phenylamino)phenyl)ethan-1-one (19)
The reaction with NiBr2•DME (77.2 mg, 0.25 mmol, 5 mol%),
Ru(bpy)3(PF6)2 (8.7 mg, 0.01 mmol, 0.2 mol%), 4’-
aminoacetophenone (2.03 g, 15 mmol, 3 equiv) and DABCO
(1.13 mg, 10 mmol, 2 equiv) was conducted in accordance
with the general procedure. Addition of DMSO (10 mL) was
followed by addition of bromobenzene (0.53 mL, 5 mmol, 1
equiv) and Et3N (1.39 mL, 10 mmol, 2 equiv) via syringe.
Total volume of the reaction mixture was 15.0 mL (5 mmol).
The reaction solution (6.0 mL) was pumped through the reac-
tor at a flow rate of 333 µL min-1 (residence time of 30 min),
irradiating with a 450 nm LED lamp with the flow wizard
program. After the reaction solution had entered the reactor, it
was followed with DMSO at the same flow rate. The crude
reaction mixture (3.00 mL, 1 mmol) from steady state was
collected in a 20 mL vial, and subsequently purified by silica
gel flash column chromatography using 40-63 µm silica gel
without the extraction process. The crude residue was purified
by flash column chromatography (10% to 30%
EtOAc/hexanes) to provide the title compound as a pale
yellow solid. (run 1: 87 mg, 41% yield; run 2: 82 mg, 39%
N-cyclohexylaniline (17)
9
The reaction with NiBr2•DME (46.3 mg, 0.15 mmol, 5 mol%),
Ru(bpy)3(PF6)2 (5.2 mg, 0.006 mmol, 0.2 mol%) and DABCO
(676 mg, 6 mmol, 2 equiv) was conducted in accordance with
the general procedure. Addition of DMSO (6 mL) was
followed by addition of bromobenzene (0.32 mL, 3 mmol, 1
equiv) and cyclohexylamine (1.72 mL, 15 mmol, 5 equiv) via
syringe. Total volume of the reaction mixture was 9.0 mL (3
mmol). The reaction solution (6.0 mL) was pumped through
the reactor at a flow rate of 167 µL min-1 (residence time of 60
min), irradiating with a 450 nm LED lamp with the flow wiz-
ard program. After the reaction solution had entered the reac-
tor, it was followed with DMSO at the same flow rate. The
crude reaction mixture (3.00 mL, 1 mmol) from steady state
was collected in a 20 mL vial, and subsequently purified by
silica gel flash column chromatography using 40-63 µm silica
gel without the extraction process. The crude residue was
purified by flash column chromatography (2% to 4% diethyl
ether/hexanes) to provide the title compound as a colorless oil.
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13
14
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16
17
18
19
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27
28
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35
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1
yield). Melting point: 95.3 – 96.0 °C. H NMR (400 MHz,
CDCl3) δ 7.87 (d, J = 8.8 Hz, 2H), 7.35 (dd, J = 7.6, 7.6 Hz,
2H), 7.19 (d, J = 7.6 Hz, 2H), 7.09 (dd, J = 7.6, 7.6 Hz, 1H),
6.99 (d, J = 8.8 Hz, 2H), 6.11 (bs, 1H), 2.53 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 196.5, 148.5, 140.7, 130.8, 129.7,
129.2, 123.5, 120.8, 114.6, 26.3. IR (neat, cm-1): 3315, 1647,
1569, 1275, 754, 575. Anal. Calcd. For C14H13NO: C, 79.59;
H, 6.20. Found: C, 79.31; H, 6.19.
1
(run 1: 119 mg, 68% yield; run 2: 112 mg, 64% yield). H
NMR (400 MHz, CDCl3) δ 7.22 – 7.15 (m, 2H), 6.69 (dd, J =
7.2, 7.2 Hz, 1H), 6.65 – 6.59 (m, 2H), 3.52 (bs, 1H), 3.28 (tt, J
= 10.1, 3.7 Hz, 1H), 2.14 – 2.05 (m, 2H), 1.85 −1.75 (m, 2H),
1.73 – 1.63 (m, 1H), 1.48 – 1.34 (m, 2H), 1.33 – 1.12 (m, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 147.5, 129.4, 116.9,
113.3, 51.8, 33.6, 26.1, 25.2. IR (neat, cm-1): 3399, 2925,
2851, 1600, 1501, 744, 691. Anal. Calcd. For C12H17N: C,
82.23; H, 9.78. Found: C, 82.25; H, 9.91.
4-phenylmorpholine (20)
The reaction with NiBr2•DME (46.3 mg, 0.15 mmol, 5 mol%),
Ru(bpy)3(PF6)2 (5.2 mg, 0.006 mmol, 0.2 mol%) and DABCO
(676 mg, 6 mmol, 2 equiv) was conducted in accordance with
the general procedure. Addition of DMSO (6 mL) was
followed by addition of bromobenzene (0.32 mL, 3 mmol, 1
equiv) and morpholine (0.79 mL, 9 mmol, 3 equiv) via
syringe. Total volume of the reaction mixture was 8.0 mL (3
mmol). The reaction solution (6.0 mL) was pumped through
the reactor at a flow rate of 333 µL min-1 (residence time of 30
min), irradiating with a 450 nm LED lamp with the flow wiz-
ard program. After the reaction solution had entered the reac-
tor, it was followed with DMSO at the same flow rate. The
crude reaction mixture (2.67 mL, 1 mmol) from steady state
was collected in a 20 mL vial, and subsequently purified by
silica gel flash column chromatography using 40-63 µm silica
gel without the extraction process. The crude residue was
purified by flash column chromatography (15% to 30% diethyl
ether/hexanes) to provide the title compound as a white solid.
(run 1: 75 mg, 46% yield; run 2: 73 mg, 45% yield). Melting
Diphenylamine (18)
The reaction with NiBr2•DME (77.2 mg, 0.25 mmol, 5 mol%),
Ru(bpy)3(PF6)2 (8.7 mg, 0.01 mmol, 0.2 mol%) and DABCO
(1.13 mg, 10 mmol, 2 equiv) was conducted in accordance
with the general procedure. Addition of DMSO (10 mL) was
followed by addition of bromobenzene (0.53 mL, 5 mmol, 1
equiv), aniline (1.37 mL, 15 mmol, 3 equiv) and Et3N (1.39
mL, 10 mmol, 2 equiv) via syringe. Total volume of the
reaction mixture was 14.6 mL (5 mmol). The reaction solution
(6.0 mL) was pumped through the reactor at a flow rate of 333
µL min-1 (residence time of 30 min), irradiating with a 450 nm
LED lamp with the flow wizard program. After the reaction
solution had entered the reactor, it was followed with DMSO
at the same flow rate. The crude reaction mixture (2.92 mL, 1
mmol) from steady state was collected in a 20 mL vial, and
subsequently purified by silica gel flash column chromatog-
raphy using 40-63 µm silica gel without the extraction pro-
cess. The crude residue was purified by flash column
chromatography (2% to 4% diethyl ether/hexanes) to provide
the title compound as a white solid. (run 1: 147 mg, 87%
yield; run 2: 147 mg, 87% yield). Melting point: 51.9 – 52.9
°C. 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.34 (m, 4H), 7.18 –
7.15 (m, 4H), 7.06 – 7.02 (m, 2H), 5.73 (bs, 1H). 13C{1H}
NMR (100 MHz, CDCl3) δ 143.2, 129.4, 121.1, 117.9. IR
1
point: 52.6 – 53.7 °C. H NMR (400 MHz, CDCl3) δ 7.40 –
7.30 (m, 2H), 6.97 – 6.91 (m, 3H), 3.91 – 3.88 (m, 4H), 3.18
(dd, J = 4.8, 4.8 Hz, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ
151.4, 129.2, 120.1, 115.7, 67.0, 49.4. IR (neat, cm-1): 1224,
1118, 924, 769, 699. Anal. Calcd. For C10H13NO: C, 73.59; H,
8.03. Found: C, 73.71; H, 8.09.
2-(dimethylamino)ethyl 4-bromobenzoate (21S)
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