The Journal of Organic Chemistry
Note
7.20 (m, 4H), 7.05 (d, J = 7.6 Hz, 4H), 4.85 (s, 2H), 2.41 (s, 6H), 2.34
(s, 3H).
was obtained as a colorless liquid. 1H NMR (400 MHz, CDCl3, ppm):
δ 7.30−7.26 (m, 4H), 7.22−7.17 (m, 6H), 3.98 (s, 2H).
N,N-Ditosyl-4-tert-butylbenzylamine (1c). Compound 1c
1-Benzyl-4-methylbenzene (3b).8 After purification of the
reaction mixture from N,N-ditosyl-4-methyl-benzylamine 1b (0.4295
g, 1.0 mmol) and phenylboronic acid 2a (0.1829 g, 1.5 mmol) by SiO2
gel flash column chromatography with hexane as the eluent, 3b
(0.1804 g, 99%) was obtained as a colorless liquid. The reaction of
N,N-ditosylbenzylamine 1a (0.4155 g, 1.0 mmol) with 4-methyl-
phenylboronic acid 2b (0.2039 g, 1.5 mmol) afforded the same
1
(1.4008 g, 99%) was obtained as a white solid. Mp 143−145 °C; H
NMR (400 MHz, CDCl3, ppm): δ 7.63 (d, J = 8.4 Hz, 4H), 7.30 (d, J
= 8.4 Hz, 2H), 7.26−7.23 (m, 2H), 7.18 (d, J = 8.0 Hz, 4H), 4.89 (s,
2H), 2.40 (s, 6H), 1.32 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3,
ppm): δ 151.2, 144.6, 137.4, 131.7, 129.4, 129.1, 128.2, 125.3, 52.3,
34.7, 31.5, 21.8; IR (vmax/cm−1): 3032, 2959, 2923, 2854, 1597, 1464,
1367, 1352, 1163, 1083, 1040, 1017, 994, 811, 788, 658, 594, 544;
HRMS (EI): m/z (M+) Calcd for C25H29NO4S2, 471.1538. Found
471.1541.
1
product (0.1803 g, 99%) as a colorless liquid. H NMR (400 MHz,
CDCl3, ppm): δ 7.31−7.28 (m, 2H), 7.22−7.19 (m, 3H), 7.130−7.08
(m, 4H), 3.96 (s, 2H), 2.33 (s, 3H).
N,N-Ditosyl-4-methoxybenzylamine (1d).9 Compound 1d
1-Benzyl-4-tert-butylbenzene (3c).2e After purification by SiO2
gel flash column chromatography with hexane as the eluent, 3c
1
(1.3092 g, 98%) was obtained as a white solid. H NMR (400 MHz,
1
CDCl3, ppm): δ 7.66−7.64 (m, 4H), 7.35−7.32 (m, 2H), 7.22 (d, J =
8.0 Hz, 4H), 6.80−6.77 (m, 2H), 4.83 (s, 2H), 3.81 (s, 3H), 2.41 (s,
6H).
(0.2223 g, 99%) was obtained as a yellowish liquid. H NMR (400
MHz, CDCl3, ppm): δ 7.34−7.28 (m, 4H), 7.23−7.19 (m, 3H), 7.15−
7.12 (m, 2H), 3.97 (s, 2H), 1.31 (s, 9H).
N,N-Ditosyl-4-chlorobenzylamine (1e).9 Compound 1e (1.2496
1-Benzyl-4-methoxybenzene (3d).8 After purification of the
reaction mixture from N,N-ditosyl-4-methoxy-benzylamine 1d (0.4556
g, 1.0 mmol) and phenylboronic acid 2a (0.1829 g, 1.5 mmol) by SiO2
gel flash column chromatography with hexane as the eluent, 3d
(0.1729 g, 87%) was obtained as a colorless liquid. The reaction of
N,N-ditosylbenzylamine 1a (0.4155 g, 1.0 mmol) with 4-methoxy-
phenylboronic acid 2d (0.2279 g, 1.5 mmol) afforded the same
1
g, 93%) was obtained as a white solid. H NMR (400 MHz, CDCl3,
ppm): δ 7.67−7.65 (m, 4H), 7.32−7.29 (m, 2H), 7.25−7.19 (m, 6H),
4.85 (s, 2H), 2.42 (s, 6H).
N,N-Ditosyl-4-bromobenzylamine (1f).9 4-Bromobenzyl amine
HCl (0.668 g, 3.0 mmol) was dissolved in H2O and treated with
Na2CO3. The reaction solution was extracted with CH2Cl2, dried over
anhydrous MgSO4, filtered, and evaporated to obtain free 4-
bromobenzylamine. The general procedure was conducted with 4-
bromobenzylamine, and 1f (1.2444 g, 83%) was obtained as a white
solid. 1H NMR (400 MHz, CDCl3, ppm): δ 7.68−7.65 (m, 4H),
7.37−7.34 (m, 2H), 7.25−7.23 (m, 6H), 4.83 (s, 2H), 2.43 (s, 6H).
N,N-Ditosyl-4-fluorobenzylamine (1g).9 Compound 1g (1.2819
1
product (0.1958 g, 98%) as a colorless liquid. H NMR (400 MHz,
CDCl3, ppm): δ 7.43−7.39 (m, 2H), 7.33−7.30 (m, 3H), 7.25−7.22
(m, 2H), 6.98−6.95 (m, 2H), 4.05 (s, 2H), 3.88 (s, 3H).
1-Benzyl-4-chlorobenzene (3e).4a After purification of the
reaction mixture from N,N-ditosyl-4-chloro-benzylamine 1e (0.4500
g, 1.0 mmol) and phenylboronic acid 2a (0.1829 g, 1.5 mmol) by SiO2
gel flash column chromatography with hexane as the eluent, 3e
(0.1610 g, 79%) was obtained as a colorless liquid. The reaction of
N,N-ditosylbenzylamine 1a (0.4155 g, 1.0 mmol) with 4-chloro-
phenylboronic acid 2e (0.2346 g, 1.5 mmol) afforded the same
1
g, 98%) was obtained as a white solid. H NMR (400 MHz, CDCl3,
ppm): δ 7.67−7.64 (m, 4H), 7.40−7.35 (m, 2H), 7.23 (d, J = 8.4 Hz,
4H), 6.97−6.91 (m, 2H), 4.85 (s, 2H), 2.42 (s, 6H).
N,N-Ditosyl-4-trifluoromethylbenzylamine (1h). Compound
1h (1.3029 g, 89%) was obtained as a white solid. Mp 136−137 °C;
1H NMR (400 MHz, CDCl3, ppm): δ 7.66 (d, J = 8.4 Hz, 4H), 7.47−
7.43 (m, 4H), 7.21 (d, J = 8.0 Hz, 4H), 4.95 (s, 2H), 2.41 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3, ppm): δ 145.0, 138.8, 136.9, 130.2
(q, J = 32 Hz), 129.5, 129.3, 128.1, 125.2 (q, J = 3.7 Hz), 124.0 (q, J =
271 Hz), 51.7, 21.6; IR (vmax/cm−1): 3065, 2923, 2853, 1619, 1595,
1492, 1445, 1350, 1324, 1161, 1112, 1068, 1048, 1004, 829, 814, 661,
546; HRMS (EI): m/z (M+) Calcd for C22H20F3NO4S2, 483.0786.
Found 483.0785.
1
product (0.1662 g, 82%) as a colorless liquid. H NMR (400 MHz,
CDCl3, ppm): δ 7.45−7.33 (m, 5H), 7.31−7.29 (m, 2H), 7.25−7.22
(m, 2H), 4.07 (s, 2H).
1-Benzyl-4-fluorobenzene (3g).8 After purification of the
reaction mixture from N,N-ditosyl-4-fluorobenzylamine 1g (0.4335 g,
1.0 mmol) and phenylboronic acid 2a (0.1829 g, 1.5 mmol) by SiO2
gel flash column chromatography with hexane as the eluent, 3g
(0.1491 g, 80%) was obtained as a yellow liquid. The reaction of N,N-
ditosylbenzylamine 1a (0.4155 g, 1.0 mmol) with 4-fluorophenyl-
boronic acid 2g (0.2100 g, 1.5 mmol) afforded the same product
5-N,N-Ditosylaminomethyl-1,3-benzodioxole (1i). Compound
1
(0.1660 g, 89%) as a yellow liquid. H NMR (400 MHz, CDCl3,
1i (1.2852 g, 93%) was obtained as a pale yellow solid. Mp 149−150
1
ppm): δ 7.31−7.27 (m, 2H), 7.22−7.16 (m, 5H), 6.98−6.94 (m, 2H),
°C (dec.); H NMR (400 MHz, CDCl3, ppm): δ 7.7 (d, J = 8.4 Hz,
3.95 (s, 2H).
4H), 7.24 (d, J = 8.0 Hz, 4H), 6.89−6.87 (m, 2H), 6.71−6.69 (m,
1H), 5.93 (s, 2H), 4.80 (s, 2H), 2.42 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 147.8, 147.5, 144.8, 137.3, 129.5, 128.7, 128.2,
123.3, 109.8, 108.0, 101.2, 52.3, 21.8; IR (vmax/cm−1): 3071, 2922,
2853, 1596, 1488, 1447, 1367, 1346, 1291, 1242, 1164, 1084, 1021,
996, 925, 828, 807, 761, 657, 538; HRMS (EI): m/z (M+) Calcd for
C22H21NO6S2, 459.0810. Found 459.0812.
1-Benzyl-4-trifluoromethylbenzene (3h).8 After purification by
SiO2 gel flash column chromatography with hexane as the eluent, 3h
1
(0.1668 g, 71%) was obtained as a colorless liquid. H NMR (400
MHz, CDCl3, ppm): δ 7.54 (d, J = 8.0 Hz, 2H), 7.33−7.29 (m, 4H),
7.25−7.21 (m, 1H), 7.19−7.17 (m, 2H), 4.04 (s, 2H).
5-Benzyl-1,3-benzodioxole (3i).8 After purification by SiO2 gel
flash column chromatography with ethyl acetate/hexane as the eluent
(1/99, v/v), 3i (0.1807 g, 85%) was obtained as a colorless liquid. 1H
NMR (400 MHz, CDCl3, ppm): δ 7.28−7.24 (m, 2H), 7.19−7.15 (m,
3H), 6.72−6.70 (m, 1H), 6.64−6.63 (m, 2H), 5.86 (s, 2H), 3.86 (s,
2H).
General Procedure for the Coupling Reaction of N,N-
Ditosylbenzylamines 1 with Arylboronic Acids 2. DPEPhos
(98%, 0.0539 g, 0.1 mmol) and Pd(CH3CN)4(BF4)2 (0.0222 g, 0.05
mmol) were added to anhydrous DMF (3.0 mL) under an argon
atmosphere in a two-necked flask, and the resulting solution was
stirred at ambient temperature for 5 min. The N,N-ditosylbenzylamine
derivative (1.0 mmol), arylboronic acid (1.5 mmol), and K2CO3
(0.4146 g, 3.0 mmol) were added, and the mixture was heated at 60
°C. When TLC indicated the absence of the N,N-ditosylbenzylamine
derivative or the color of the reaction solution turned dark brown, the
mixture was cooled to ambient temperature. The solution was
extracted with hexane, washed with brine, dried over anhydrous
MgSO4, filtered, and evaporated to afford the crude mixture. The
crude product mixture was purified by SiO2 gel flash column
chromatography (ethyl acetate/hexane) to yield the diarylmethane.
Diphenylmethane (3a).8 After purification by SiO2 gel flash
column chromatography with hexane as the eluent, 3a (0.1615 g, 96%)
4-Benzylphenol (3j).2e After purification by SiO2 gel flash column
chromatography with ethyl acetate/hexane as the eluent (1/7, v/v), 3j
1
(0.1660 g, 90%) was obtained as a pale yellow solid. H NMR (400
MHz, CDCl3, ppm): δ 7.30−7.23 (m, 2H), 7.18−7.13 (m, 3H), 7.02−
7.00 (m, 2H), 6.72−6.70 (m, 2H), 5.44 (br. s, 1H), 3.87 (s, 2H).
4-Benzylbenzaldehyde (3k).2b After purification by SiO2 gel
flash column chromatography with ethyl acetate/hexane as the eluent
1
(1/7, v/v), 3k (0.1943 g, 99%) was obtained as a yellow liquid. H
NMR (400 MHz, CDCl3, ppm): δ 9.95 (s, 1H), 7.79 (d, J = 8.0 Hz,
2H), 7.34−7.28 (m, 4H), 7.24−7.16 (m, 3H), 4.04 (s, 2H).
Methyl 4-Benzylbenzoate (3l).8 After purification by SiO2 gel
flash column chromatography with ethyl acetate/hexane as the eluent
4210
dx.doi.org/10.1021/jo500462n | J. Org. Chem. 2014, 79, 4206−4211