2482 J . Org. Chem., Vol. 66, No. 7, 2001
Notes
with CH2Cl2 (30 mL), the combined organic layers were dried
over sodium sulfate, and the solvent was removed in vacuo.
Amine 2b (1.21 g, 80%) was obtained as yellow, highly viscous
oil: Rf (SiO2, 35% aq NH3/MeOH 1:10) 0.38; 1H NMR δ 3.24 (m,
4H), 3.12 (m, 4H), 2.74 (t, 4H, 3J ) 6.60 Hz), 1.62 (m, 4H), 1.70-
N1,N2-Di(ter t-bu tyloxycar bon yl)-N1,N2-di(3-am in opr opyl)-
1,2-cycloh exa n ed ia m in e (2f). Nitrile 1f (500 mg, 1.19 mmol)
was dissolved in a mixture of dioxane (20 mL) and water (5 mL).
Raney-nickel (200 mg, 1.70 mmol) as a 50% suspension in water
and 10% palladium on charcoal (120 mg, 0.113 mmol) were
added together with lithium hydroxide monohydrate (150 mg,
3.57 mmol), and the reaction mixture was stirred under hydro-
gen atmosphere at 50 °C for 20 h. The catalysts were filtered
off, the solvents were removed in vacuo, and a mixture of water
(50 mL) and CH2Cl2 (25 mL) was added. After phase separation,
the aqueous phase was extracted twice with CH2Cl2 (15 mL),
the combined organic layers were dried over sodium sulfate, and
the solvent was removed in vacuo. Amine 2f (480 mg, 94%) was
obtained as colorless, highly viscous oil: Rf (SiO2, 35% aq NH3/
MeOH 1:10) 0.47; 1H NMR δ 4.11-3.97/3.85-3.56 (2m, 2H),
3.29-3.01/2.94-2.76 (2m, 4H), 2.61 (t, 4H, 3J ) 6.86 Hz), 1.93-
1.76 (m, 2H), 1.76-1.59 (m, 4H), 1.50-1.30 (m, 6H, NH among
here), 1.42 (s, 18H), 1.30-1.15 (m, 4H); 13C NMR δ 155.8 (s),
79.3 (s), 55.1 (d), 41.2 (t), 40.3 (t), 34.9 (t), 31.3 (t), 28.6 (q), 25.5
(t); MS m/z 429 (M + H+, 100), 329 (M - Boc + 2H+, 10); HRMS
calcd for C22H45N4O4+ 429.3441, found 429.3435. Column chro-
matography on SiO2 using Et3N/MeOH 1:10 as eluent afforded
an analytically pure sample. Anal. Calcd for C22H45N4O4: C,
61.65; H, 10.35; N, 13.07. Found: C, 61.27; H, 10.29; N, 12.88.
1.57 (m, 4H, NH2), 1.50-1.42 (m, 22H), 1.35-1.30 (m, 6H); 13
C
NMR δ 156.0 (s), 79.5 (s), 47.1 (t), 44.2 (t), 39.6 (t), 32.8 (t), 32.2
(t), 29.6 (t), 27.3 (t), 28.7 (q); MS m/z 467 (M + Na+, 23), 445 (M
+
+ H+, 100), 223 ((M + 2H+)/2, 30); HRMS calcd for C23H49N4O4
445.3754, found 445.3753.
N1,N9-Di(ter t-bu tyloxycar bon yl)-N1,N9-di(3-am in opr opyl)-
1,9-n on a n ed ia m in e (2c). Nitrile 1c (1.15 g, 2.48 mmol) was
dissolved in a mixture of dioxane (80 mL) and water (20 mL).
Raney-nickel (550 mg, 4.69 mmol) as a 50% suspension in water
and 10% palladium on charcoal (165 mg, 0.155 mmol) were
added together with lithium hydroxide monohydrate (225 mg,
5.36 mmol), and the reaction mixture was stirred under hydro-
gen atmosphere at 50 °C for 18 h. The catalyst was filtered off,
the solvents were removed in vacuo, and a mixture of water (100
mL) and CH2Cl2 (30 mL) was added. After phase separation,
the aqueous phase was extracted three times with CH2Cl2 (30
mL), the combined organic layers were dried over sodium sulfate,
and the solvent was removed in vacuo. Amine 2c (1.01 g, 86%)
was obtained as a yellow, highly viscous oil: Rf (SiO2, 35% aq
NH3/MeOH 1:10) 0.38; 1H NMR δ 3.22 (m, 4H), 3.10 (m, 4H),
2.64 (t, 4H, 3J ) 6.59 Hz), 1.61 (m, 4H), 1.68-1.55 (m, 4H, NH2),
1.42 (m, 22H), 1.24 (m, 10H); 13C NMR δ 155.9 (s), 79.3 (s), 47.0
(t), 44.5 (t), 43.9 (t), 39.5 (t), 39.3 (t), 32.7 (t), 31.9 (t), 29.7 (t),
29.4 (t), 28.6 (q), 27.0 (t); MS m/z 473 (M + H+, 20), 237 ((M +
2H+)/2, 30), 181 ((M + 3Na+)/3, 30), 159 ((M + 3H+)/3, 30), 137
N1,N4-Di(ter t-bu tyloxycar bon yl)-N1,N4-di(3-am in opr opyl)-
1,4-cycloh exa n ed ia m in e (2g). Nitrile 1g (1.67 g, 3.97 mmol)
was dissolved in a mixture of dioxane (40 mL) and water (10
mL). Raney-nickel (500 mg, 4.26 mmol) as a 50% suspension in
water and 10% palladium on charcoal (400 mg, 0.376 mmol) were
added together with lithium hydroxide monohydrate (450 mg,
10.7 mmol), and the reaction mixture was stirred under hydro-
gen atmosphere at 50 °C for 20 h. The catalysts were filtered
off, the solvents were removed in vacuo, and a mixture of water
(100 mL) and CH2Cl2 (30 mL) was added. After phase separation,
the aqueous phase was extracted four times with CH2Cl2 (30
mL), the combined organic layers were dried over sodium sulfate,
and the solvent was removed in vacuo. Amine 2g (1.53 g, 90%)
was obtained as yellow, highly viscous oil: Rf (SiO2, 35% aq NH3/
MeOH 1:10) 0.29; 1H NMR δ 3.54-3.24 (m, 2H), 3.20-2.97 (m,
4H), 2.68-2.48 (m, 4H), 1.72 (m, 4H, NH2), 1.59 (m, 8H), 1.47-
1.32 (m, 4H); 13C NMR δ 155.6 (s), 79.5 (s), 56.0 (d), 54.2 (d),
41.5 (t), 39.7 (t), 34.8 (t), 30.1 (t), 28.6 (q); MS m/z 429 (M + H+,
+
(100); HRMS calcd for C25H53N4O4 473.4067, found 473.4063.
N1,N12-Di(ter t-bu tyloxyca r bon yl)-N1,N12-d i(3-a m in op r o-
p yl)-1,12-d od eca n ed ia m in e (2d ). Nitrile 1d (800 mg, 1.58
mmol) was dissolved in a mixture of dioxane (20 mL) and water
(5 mL). Raney-nickel (200 mg, 1.70 mmol) as a 50% suspension
in water and 10% palladium on charcoal (165 mg, 0.155 mmol)
were added together with lithium hydroxide monohydrate (135
mg, 3.22 mmol), and the reaction mixture was stirred under
hydrogen atmosphere at 50 °C for 20 h. The catalysts were
filtered off, the solvents were removed in vacuo, and a mixture
of water (50 mL) and CH2Cl2 (25 mL) was added. After phase
separation, which was accelerated by addition of sodium chlo-
ride, the aqueous phase was extracted three times with CH2Cl2
(15 mL), the combined organic layers were dried over sodium
sulfate, and the solvent was removed in vacuo. Amine 2d (750
mg, 92%) was obtained as light yellow oil: Rf (SiO2, 35% aq NH3/
100), 329 (M - Boc + 2H+, 50); HRMS calcd for C22H45N4O4
429.3441, found 429.3445.
+
N1,N2-Di(3-a m in op r op yl)-1,2-ben zen ed ia m in e (2h ). Ni-
trile 1h (500 mg, 2.33 mmol) was dissolved in a mixture of
dioxane (20 mL) and water (5 mL). Raney-nickel (270 mg, 2.30
mmol) as a 50% suspension in water and 10% palladium on
charcoal (200 mg, 0.188 mmol) were added together with lithium
hydroxide monohydrate (200 mg, 4.77 mmol), and the reaction
mixture was stirred under hydrogen atmosphere at 50 °C for
20 h. The catalysts were filtered off and rinsed with a mixture
of dioxane (20 mL) and water (10 mL), and the solvents were
removed from the filtrate in vacuo. A mixture (530 mg) of LiOH
and amine 2h was obtained as a brownish highly viscous oil:
Rf (SiO2, 35% aq NH3/MeOH 1:10) baseline; 1H NMR δ 6.70-
6.59 (m, 4H), 3.13 (t, 4H, 3J ) 6.95 Hz), 2.76 (t, 4H, 3J ) 7.04
Hz), 1.80 (tt, 4H, 3J ) 6.95, 3J ) 7.04 Hz), NH exchanged; 13C
NMR δ 138.3 (s), 119.7 (d), 112.5 (d), 43.2 (t), 40.7 (t), 33.5 (t);
MS m/z 229 (M + Li+, 50), 223 (M + H+, 100); HRMS calcd for
1
MeOH 1:10) 0.40; H NMR δ 3.24 (m, 4H), 3.12 (m, 4H), 2.67-
2.59 (m, 4H), 1.85 (m, 4H, NH2), 1.63 (m, 4H), 1.55-1.38 (m,
4H), 1.44 (s, 18H), 1.25 (m, 16H); 13C NMR δ 156.0 (s) 155.7 (s),
79.2 (s), 47.0 (t), 44.1 (t), 39.2 (t), 32.0 (t), 29.7 (t), 29.6 (t) 29.5
(t), 28.5 (q), 27.0 (t); MS m/z 515 (M + H+, 100); HRMS calcd
for C28H59N4O4+ 515.4536, found 515.4540. Column chromatog-
raphy on SiO2 using Et3N/MeOH 1:10 as eluent afforded an
analytically pure sample. Anal. Calcd for C28H58N4O4: C, 65.33;
H, 11.36; N, 10.88. Found: C, 64.98; H, 11.19; N, 10.49.
N1,N2-Di(ter t-bu tyloxycar bon yl)-N1,N2-di(3-am in opr opyl)-
1,2-p r op a n ed ia m in e (2e). Nitrile 1e (500 mg, 1.31 mmol) was
dissolved in a mixture of dioxane (20 mL) and water (5 mL).
Raney-nickel (200 mg, 1.70 mmol) as a 50% suspension in water
and 10% palladium on charcoal (120 mg, 0.113 mmol) were
added together with lithium hydroxide monohydrate (170 mg,
4.05 mmol), and the reaction mixture was stirred under hydro-
gen atmosphere at 50 °C for 20 h. The catalysts were filtered
off, the solvents were removed in vacuo, and a mixture of water
(50 mL) and CH2Cl2 (25 mL) was added. After phase separation,
the aqueous phase was extracted twice with CH2Cl2 (15 mL),
the combined organic layers were dried over sodium sulfate, and
the solvent was removed in vacuo. Amine 2e (430 mg, 84%) was
obtained as a colorless, highly viscous oil: Rf (SiO2, 35% aq NH3/
MeOH 1:10) 0.36; 1H NMR δ 4.18-3.71 (m, 1H), 3.53-2.94 (m,
6H), 2.72-2.56 (m, 4H), 1.60 (m, 4H), 1.42 (s, 18H), 1.33 (s, 4H,
+
C12H23N4 223.1922, found 223.1926.
N1,N3-Di(3-a m in op r op yl)-1,3-ben zen ed ia m in e (2i). Nitrile
1i (500 mg, 2.33 mmol) was dissolved in a mixture of dioxane
(20 mL) and water (5 mL). Raney-nickel (270 mg, 2.30 mmol)
as a 50% suspension in water and 10% palladium on charcoal
(270 mg, 0.254 mmol) were added together with lithium hydrox-
ide monohydrate (200 mg, 4.77 mmol), and the reaction mixture
was stirred under hydrogen atmosphere at 50 °C for 20 h. The
catalysts were filtered off and rinsed with a mixture of dioxane
(20 mL) and water (10 mL), and the solvents were removed from
the filtrate in vacuo. A mixture (560 mg) of LiOH and amine 2i
was obtained as a brownish solid: Rf (SiO2, 35% aq NH3/MeOH
1:10) baseline; 1H NMR δ 6.88 (m, 1H), 6.14-5.99 (m, 1H), 6.02
(m, 2H), 3.09 (t, 4H, 3J ) 6.95 Hz), 2.72 (t, 4H, 3J ) 7.04 Hz),
1.74 (tt, 4H, 3J ) 6.95 Hz, 3J ) 7.04 Hz), NH exchanged; 13C
NMR δ 151.2 (s), 130.6 (d), 104.4 (d), 99.3 (d), 42.8 (t), 40.5 (t),
3
NH2), 1.13 (d, 3H, J ) 6.40 Hz); 13C NMR δ 155.6 (s), 79.7 (s),
52.6 (d), 51.7 (d), 50.8 (d), 49.9 (t), 49.1 (t), 45.5 (t), 44.9 (t), 44.2
(t), 43.8 (t), 43.5 (t), 40.0 (t), 39.7 (t), 39.4 (t), 34.3 (t), 33.5 (t),
32.7 (t), 31.9 (t), 28.6 (q), 17.2 (q), 16.2 (q); MS m/z 411 (M +
Na+, 36), 389 (M + H+, 60), 195 ((M + 2H+)/2, 12); HRMS calcd
+
for C19H41N4O4 389.3128, found 389.3131.