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indicated completion of the reaction. The reaction mixture was quenched
with deionized water (10 mL), and the mixture was extracted with
Et2O (3 × 10 mL). The combined organic layers were dried with
anhydrous MgSO4, filtered, and evaporated in vacuo (25 °C, 1
Torr) to afford the reduced propylbenzene product as a colorless oil
(0.278 g, 77% yield).
(d, 1H, J = 8); 13C NMR (125 MHz, CDCl3) δ 47.1, 123.6, 127.9,
128.6, 129.2, 132.9, 142.3.
3-Chlorobenzylamine (Table 3, Entry 5).23 Yellowish oil (0.371 g,
87% yield): 1H NMR (500 MHz, CDCl3) δ 1.52 (s, 2H), 3.82 (s, 2H),
7.18−7.30 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 46.0, 125.3,
126.9, 127.3, 129.9, 134.4, 145.4.
Propylbenzene.22 Colorless oil (0.278 g, 77% yield): 1H NMR
(500 MHz, CDCl3) δ 1.01 (t, 3H, J = 7.5), 1.72 (m, 2H), 2.65 (t, 2H,
J = 7.5), 7.24 (m, 3H), 7.34 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 13.9, 24.7, 38.2, 125.8, 128.3, 128.5, 142.7.
2-Chloro-6-fluorobenzylamine (Table 3, Entry 6).6 Yellowish oil
1
(0.361 g, 75% yield): H NMR (500 MHz, CDCl3) δ 1.74 (bs, 2H),
3.96 (s, 2H), 6.96 (m, 1H), 7.15 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 37.5, 114.3, 125.5, 128.8, 134.9, 160.4, 162.4.
4.5. General Procedure for the InCl3/NaBH4 Studies (Scheme 1).
The following procedure for the reaction of InCl3/NaBH4 is
representative. An oven-dried round-bottom flask (25 mL) cooled
under argon was fitted with a rubber septum and charged with a stir
bar, anhydrous InCl3 (0.663 g, 3 mmol), anhydrous THF (10 mL),
and NaBH4 (0.11 g, 3 mmol). The reaction was then stirred at 25 °C
for 1 h, and an aliquot was taken and analyzed by 11B NMR
spectroscopy. A similar procedure was followed when using CH3CN
and dimethyl sulfide as a solvent (see Scheme 1).
2,3-Dichlorobenzylamine (Table 3, Entry 7).6 Yellowish oil (0.395
1
g, 75% yield): H NMR (500 MHz, CDCl3) δ 1.75 (bs, 2H), 3.86
(s, 2H), 7.19 (m, 1H), 7.29 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 43.9, 127.4, 129.4, 129.8, 133.3, 133.9 139.2.
Phenethylamine (Table 3, Entry 8).6 Yellowish oil (0.255 g, 70%
1
yield): H NMR (500 MHz, CDCl3) δ 1.44 (s, 2H), 2.74 (t, 2H,
J = 6.5), 2.96 (t, 2H, J = 6.5) 7.21 (m, 3H), 7.30 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 40.0, 43.5, 126.2, 128.5, 128.9, 139.9.
2-(4-Methoxyphenyl)ethanamine (Table 3, Entry 9).6 Yellowish
oil (0.362 g, 80% yield): 1H NMR (500 MHz, CDCl3) δ 1.26 (bs, 2H),
2.67 (t, 2H, J = 7), 2.91 (t, 2H, J = 7), 3.76 (s, 3H), 6.83 (d, 2H,
J = 6.5), 7.10 (d, 2H, J = 8.5); 13C NMR (125 MHz, CDCl3) δ 39.1,
43.7, 55.2, 113.9, 129.8, 131.9, 158.1.
4.6. InCl3/NaBH4 Reduction of the Carbon Bromine Bond.
An oven-dried round-bottom flask (25 mL) cooled under argon was fitted
with a rubber septum and charged with a stir bar, anhydrous InCl3 (0.663
g, 3 mmol), anhydrous THF (10 mL), and NaBH4 (0.34 g, 9 mmol).
The reaction was stirred at 25 °C for 1 h. (3-Bromopropyl)benzene
(0.456 mL, 3 mmol) was then added dropwise, and the mixture was
stirred at 25 °C. After 4 h, thin layer chromatography analysis indicated
completion of the reaction. The reaction was quenched with deionized
water (10 mL), and the mixture was extracted with Et2O (3 × 10 mL).
The combined organic layers were dried with anhydrous MgSO4, filtered,
and evaporated in vacuo (25 °C, 1 Torr) to afford the reduced
propylbenzene product as a colorless oil (0.289 g, 80% yield).
Heptylamine (Table 3, Entry 10).24 Yellowish oil (0.297 g, 86%
yield): 1H NMR (500 MHz, CDCl3) δ 0.87 (t, 3H, J = 7), 1.28
(m, 8H), 1.41 (m, 2H) 1.51 (bs, 2H), 2.67 (t, 2H, J = 6.5); 13C NMR
(125 MHz, CDCl3) δ 14.1, 22.6, 26.9, 29.2, 31.8, 33.6, 42.1.
Cyclohexanemethylamine (Table 3, Entry 11).25 Yellowish oil
1
(0.248 g, 72% yield): H NMR (500 MHz, CDCl3) δ 0.85 (m, 2H),
1.2 (m, 4H), 1.30 (s, 2H), 1.70 (m, 5H), 2.49 (d, 2H); 13C NMR (125
MHz, CDCl3) δ 26.1, 26.7, 30.8, 41.3, 48.9.
Propylbenzene.22 Colorless oil (0.289 g, 80% yield).
2-(3-Thienyl)ethanamine (Table 3, Entry 12).26 Yellowish oil
1
4.7. General Procedure for the Reduction of Aromatic,
Benzyl, and Aliphatic Nitriles (Table 3, Entries 1−13). The
following procedure for the reduction of benzonitrile by InCl3/NaBH4
is representative. An oven-dried round-bottom flask (25 mL) cooled
under argon was fitted with a rubber septum and charged with a stir
bar, anhydrous InCl3 (0.663 g, 3 mmol), anhydrous THF (10 mL),
and NaBH4 (0.34 g, 9 mmol). The reaction was stirred at 25 °C for
1 h, followed by the dropwise addition of benzonitrile (0.306 mL,
3 mmol), and the mixture was stirred at 25 °C. After 4 h at 25 °C, thin
layer chromatography analysis and infrared spectroscopy indicated
completion of the reaction. The solution was quenched with 3 M
hydrochloric acid (10 mL), and the solution was refluxed for 1 h to
dissolve remaining metal salts. The reaction mixture was cooled to
25 °C, methanol (5 mL) was added, and the mixture was again refluxed
for 1 h. The reaction mixture was then cooled to 25 °C and filtered,
and the methyl borate/methanol was removed from the filtrate by
evaporation. The remaining acidic solution was extracted with Et2O/
THF (3 × 10 mL), and the organic layers were discarded. The acidic
aqueous layer was then basified with NaOH pellets to pH ∼ 10 and
again extracted with a 1:1 mixture of Et2O/THF (3 × 10 mL). The
combined organic layers were dried with anhydrous MgSO4, filtered,
and evaporated in vacuo (25 °C, 1 Torr) to afford the benzylamine
product as a yellowish oil (0.242 g, 75% yield).
(0.372 g, 97% yield): H NMR (500 MHz, CDCl3) δ 1.59 (bs, 2H),
2.75 (t, 2H, J = 6.5), 2.93 (t, 2H, J = 6.5), 6.93 (m, 1H), 6.97 (m, 1H),
7.26 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 34.4, 42.7, 121.2,
125.8, 128.3, 140.2.
2-(2-Thienyl)ethanamine (Table 3, Entry 13).27 Yellowish oil
1
(0.375 g, 98% yield): H NMR (500 MHz, CDCl3) δ 1.42 (bs, 2H),
2.98 (m, 4H, J = 8), 6.85 (m, 1H), 6.95 (m, 1H), 7.16 (m, 1H); 13C
NMR (125 MHz, CDCl3) δ 33.2, 40.4, 126.8, 128.3, 128.5, 136.6.
4.8. Tandem Reduction of 4-(Bromomethyl)benzonitrile
Using InCl3/NaBH4 in THF (Scheme 3). An oven-dried round-
bottom flask (25 mL) cooled under argon was fitted with a rubber
septum and charged with a stir bar, anhydrous InCl3 (0.663 g,
3 mmol), anhydrous THF (10 mL), and NaBH4 (0.34 g, 9 mmol).
The reaction was then stirred at 25 °C for 1 h, at which time
4-(bromomethyl)benzonitrile (0.588 g, 3 mmol) was added to the
reaction mixture and stirred. After 4 h, thin layer chromatography
analysis and infrared spectroscopy indicated completion of the
reaction. The reaction was quenched with 3 M hydrochloric acid
(10 mL), and the solution was refluxed for 1 h. The reaction mixture
was cooled to 25 °C, methanol (5 mL) was added, and the mixture
was again refluxed for 1 h. The reaction mixture was again cooled to
25 °C and then filtered, and the methyl borate was removed from the
filtrate by evaporation. The remaining acidic solution was extracted
with a 1:1 mixture of Et2O/THF (3 × 10 mL), and the organic layers
were discarded. The acidic aqueous layer was then basified with NaOH
pellets to pH ∼ 10 and again extracted with a 1:1 mixture of Et2O/
THF (3 × 10 mL). The combined organic layers were dried over
anhydrous MgSO4, filtered, and evaporated in vacuo (25 °C, 1 Torr)
to afford the tandem reduction 4-methylbenzylamine product as a
slightly yellowish oil (0.287 g, 61% yield). 6-Bromohexanenitrile also
underwent a similar tandem reduction under the same reaction
conditions to afford hexylamine as a colorless oil (0.206 g, 68% yield).
4-Methylbenzylamine.6 Colorless oil (0.287 g, 61% yield): 1H
NMR (500 MHz, CDCl3) δ 1.73 (bs, 2H), 2.35 (s, 3H), 3.80 (s, 2H),
7.16 (d, 2H, J = 8), 7.21 (d, 2H, J = 8.5); 13C NMR (125 MHz,
CDCl3) δ 21.0, 46.3, 127.2, 129.4, 136.5, 140.4.
Benzylamine (Table 3, Entry 1).6 Yellowish oil (0.242 g, 75%
1
yield): H NMR (500 MHz, CDCl3) δ 1.85 (s, 2H), 3.86 (s, 2H),
7.25−7.36 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 46.5, 126.9,
127.3, 128.7, 143.3.
4-Methylbenzylamine (Table 3, Entry 2).6 Colorless oil (0.287 g,
79% yield): 1H NMR (500 MHz,CDCl3) δ 1.73 (bs, 2H), 2.35
(s, 3H), 3.80 (s, 2H), 7.16 (d, 2H, J = 8), 7.21 (d, 2H, J = 8.5); 13C
NMR (125 MHz, CDCl3) δ 21.0, 46.3, 127.2, 129.4, 136.5, 140.4.
4-Methoxybenzylamine (Table 3, Entry 3).6 Yellowish oil (0.344
1
g, 83% yield): H NMR (500 MHz, CDCl3) δ 1.54 (bs, 2H), 3.80
(s, 5H), 6.87 (d, 2H, J = 9 Hz), 7.23 (d, 2H); 13C NMR (125 MHz,
CDCl3) δ 46.0, 55.4, 114.1, 128.4, 135.7, 158.7.
2-Bromobenzylamine (Table 3, Entry 4).6 Yellowish oil (0.439 g,
80% yield): 1H NMR (500 MHz, CDCl3) δ 1.79 (s, 2H), 3.89 (s, 2H),
7.10 (t, 1H, J = 7.5), 7.28 (t, 1H, J = 7.5), 7.35 (d, 1H, J = 7.75), 7.54
Hexylamine.24 Colorless oil (0.206 g, 76% yield): H NMR (500
1
MHz, CDCl3) δ 0.84 (m, 3H), 1.25 (m, 6H), 1.38 (m, 2H), 1.64 (bs, 2H),
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dx.doi.org/10.1021/jo201809a | J. Org. Chem. 2012, 77, 221−228