One-Pot Three-Component Solvent-Free Syntheses
Letters in Organic Chemistry, 2010, Vol. 7, No. 4
303
°C) overnight. The formed oil was separated by decantation.
The combined products were recrystallized twice from
acetonitrile (40 mL). Compound 5 was obtained as white
powder. Yield 1.3 g (33 %).
1H NMR (CDCl3, 500 MHz, ppm): 7.1 (s, 4H, aryl-OH),
6.85 (s, 4H, aryl H), 6.72 (s, 4H, aryl H), 3.65 (s, 8H, N-
CH2-aryl), 2.47 (t, J = 7 Hz, 4H, N-CH2-alkyl), 2.22 (s, 12H,
aryl-CH3), 2.17 (s, 12H, aryl-CH3), 1.57 (m, J = 7 Hz, 4H,
alkyl CH2), 1.24 (m, J = 7 Hz, 4H, alkyl CH2) and 1.18 (m, J
= 7 Hz, 2H, alkyl CH2).
thermal oven at 120 °C the yellowish product was dissolved
in hot acetonitrile (40 mL) and the solution was stored in a
refrigerator (7 °C) overnight. The formed solid was
decantated and recrystallized twice from acetonitrile (40 mL)
in a refrigerator. Compound 7 was obtained as white powder.
Yield 2.3 g (56 %).
1H NMR (CDCl3, 500 MHz, ppm): 8.3 (s, 4H, aryl-OH),
6.83 (s, 4H, aryl H), 6.73 (d, J = 2 Hz, 4H, aryl H), 3.64 (s,
8H, N-CH2-aryl), 2.52 (t, J = 7 Hz, 4H, N-CH2-alkyl), 2.22
(s, 12H, aryl-CH3), 2.07 (s, 12H, aryl-CH3), 1.60 (m, J = 7
Hz, 4H, alkyl CH2), 1.46 (m, J = 7 Hz, 4H, alkyl CH2) and
1.26 (m, J = 7 Hz, 4H, alkyl CH2).
13C NMR (CDCl3, 126 MHz, ppm): 152, 131, 129, 128,
124, 122 (aryl C), 56.1 (N-CH2-aryl), 53.4 (N-CH2-alkyl),
29.1, 27.0 and 26.1 (alkyl C), 20.4 and 15.9 (aryl-CH3).
13C NMR (CDCl3, 126 MHz, ppm): 152, 131, 129, 128,
124, 122 (aryl C), 55.9 (N-CH2-aryl), 54.1 (N-CH2-alkyl),
30.0, 26.9 and 26.8 (alkyl C), 20.3 and 16.1 (aryl-CH3).
ESI-TOF MS 667.4470 [M+H]+. The calculated value
667.4475 [M+H]+.
ESI-TOF MS 681.4644 [M+H]+. The calculated value
Elemental anal. for 5: Calc. for C43H58N2O4: C, 77.4; H,
8.77; N, 4.20. Found: C, 77.3; H, 8.85; N, 4.22. Single
crystals of 5 were prepared by dissolving 90 mg of white
powder product in acetonitrile (10 mL) in a test tube and
placing the tube in a freezer (-17 °C) overnight. One
colourless single crystal was analyzed by X-ray diffraction.
653.4631 [M+H]+.
Elemental anal. for 7: Calc. for C44H60N2O4: C, 77.5; H,
8.88; N, 4.11. Found: C, 77.3; H, 8.87; N, 4.24.
N,N,N’N’-tetra(2-hydroxy-5-t-butyl-3-methylbenzyl)-1,8-
diamino-octane (8)
N,N,N’,N’-tetra(2-hydroxy-5-t-butyl-3-methylbenzyl)-1,7-
diaminoheptane•2HCl (6•2HCl)
The crude material of 8 was prepared as that of 2 using
1,8-diamino-octane (0.433 g, 3 mmol). After reaction in a
thermal oven at 120 °C the yellowish product was dissolved
in hot acetonitrile (15 mL) and water was dropwise added
(500 ꢀL). The solution was left to stand in a refrigerator (7
°C) for 3 hours after which the top layer of the cold solution
was separated by decantation. The top layer was discarded,
and the yellow bottom layer was dissolved in
dichloromethane (5 mL) and acetonitrile (15 mL) was added.
The solution was placed in a freezer (-20 °C) and filtered
after 7 hours. The product was recrystallized in a CH2Cl2-
MeCN (1:3) mixture as previously described. Compound 8
was allowed to dry in open air and obtained as a white
powder. Yield 0.86 g, 34 %.
1H NMR (DMSO-d6, 500 MHz, ppm): 9.52 (s, 4H, aryl-
OH), 6.97 (d, J = 2 Hz, 4H, aryl H), 6.92 (d, J = 2 Hz, 4H,
aryl H), 3.62 (s, 8H, N-CH2-aryl), 2.36 (t, J = 7 Hz, 4H, N-
CH2-alkyl), 2.12 (s, 12H, aryl-CH3), 1.44 (m, J = 7 Hz, 4H,
alkyl CH2), 1.20 (s, 36H, aryl t-butyl), 1.03 (m, J = 7 Hz, 8H,
alkyl CH2).
The crude product was obtained similarly to compound 2
using 1,7-diaminoheptane (0.781 g, 6 mmol), 4-t-butyl-2-
methylphenol (30 mmol, 24 mmol equiv.) and
paraformaldehyde (30 mmol, 24 mmol equiv.). After the
thermal oven treatment, the product was dissolved in boiling
acetonitrile (20 mL) and 6 M HCl (4.0 mL, double amount)
and water (1.0 mL) were added. The cooled solution was
vigorously stirred for 10 minutes and allowed to settle down
at RT for 1.5 hours and the precipitate was filtered off. A
small amount of product was separated from the filtrate after
4 hours and was added to main product. Finally the solid was
dissolved in hot MeOH (10 mL) and acetonitrile (35 mL)
was added. The vessel was kept in a freezer (-17 °C)
overnight and 6•2HCl was collected by filtration. Yield 1.9
g, 35 %.
1H NMR (MeOD, 500 MHz, ppm): 7.24 (d, J = 2 Hz, 4H,
aryl H), 7.17 (d, J = 2 Hz, 4H, aryl H), 4.38 (s, 8H, N-CH2-
aryl), 3.09 (t, J = 8 Hz, 4H, N-CH2-alkyl), 2.26 (s, 12H, aryl-
CH3), 1.73 (m, J = 7 Hz, 4H, alkyl CH2), 1.28 (m, 36H, aryl
t-butyl), 1.19 (m, J = 7 Hz, 4H, alkyl CH2), 1.10 (m, J = 7
Hz, 2H, alkyl CH2).
13C NMR (DMSO-d6, 126 MHz, ppm): 152, 141, 126,
124, 123, 122 (aryl C), 54.6 (N-CH2-aryl), 52.4 (N-CH2-
alkyl), 33.4 and 31.3 (t-butyl C), 28.5, 26.5 and 25.1 (alkyl
C), 16.3 (aryl-CH3).
13C NMR (MeOD, 126 MHz, ppm): 153, 145, 131, 128,
126, 119 (aryl C), 57.2 (N-CH2-aryl), 54.2 (N-CH2-alkyl),
35.0 and 32.0 (t-butyl C), 29.3, 27.1 and 25.0 (alkyl C), 16.9
(aryl-CH3).
ESI-TOF MS 849.6473 [M+H]+. The calculated value
849.6509 [M+H]+.
Compound 8 was crystallized twice from a CH2Cl2-
MeCN (1:3) mixture and heated at 90 °C in a thermal oven
before elemental analysis. Elemental anal. for 8: Calc. for
C56H84N2O4: C, 79.2; H, 9.97; N, 3.30. Found: C, 78.9; H,
9.93; N, 3.19.
ESI-TOF MS 835.6313 [M+H]+. The calculated value
835.6353 [M+H]+.
Elemental anal. for 6•2HCl. Calc. for C55H84N2O4Cl2: C,
72.7; H, 9.32; N, 3.08. Found: C, 72.0; H, 9.39; N, 3.25.
N,N,N’N’-tetra(2-hydroxy-3,5-dimethylbenzyl)-1,8-diamino-
octane (7)
In the synthesis of compound 8•2HCl the amounts of
starting materials and heating in a thermal oven were the
same as those for the HCl free compound. The yellow solid
from the thermal oven was dissolved in boiling acetonitrile
(10 mL) and 6 M HCl (2 mL, double amount) was added.
The crude material of 7 was prepared as that of 1 using
1,8-diamino-octane (0.866 g, 6 mmol). After reaction in a