Thioether-Based Tris-Melamines
J . Org. Chem., Vol. 61, No. 5, 1996 1785
N-[[4-(1,1-d im eth yleth yl)p h en yl]m eth yl]ben za m id e (14).
A 250-mL round-bottomed flask was charged with 6.00 g (17.34
mmol) of compound 133 and 40 mL of thionyl chloride. The
mixture was heated at reflux with stirring under a nitrogen
atmosphere for 2 h. The reaction mixture was cooled to room
temperature and diluted with 100 mL of toluene, and the
solvent and the excess thionyl chloride were removed in vacuo.
The residue was again dissolved in 100 mL of toluene, concd,
and dried in vacuo. The resulting acid chloride was dissolved
in 50 mL of methylene chloride and 100 mL of toluene. The
solution was cooled in an ice bath, and 7.05 g (9.72 mL, 69.60
mmol) of triethylamine was added, followed by 6.66 g (17.36
mmol) of 12. The mixture was allowed to warm to room
temperature, stirred for 2 h, and diluted with 150 mL of
toluene. This solution was washed with 150 mL of water,
twice with 150-mL portions of saturated aqueous sodium
carbonate, 200 mL of water, and 150 mL of brine. The solution
was dried over MgSO4, and the solvent was removed by rotary
evaporation. The residue was purified by column chromatog-
raphy (eluted with 33:66 ethyl acetate/hexanes) to give 10.63
g (14.93 mmol, 86%) of the product as a white foam: Rf 0.48
(33:66 ethyl acetate/hexanes); 1H NMR (500 MHz, DMSO-d6)
δ 8.03-7.93 (m, 4H), 7.68 (d, J ) 7.1 Hz, 1H), 7.40 (d, J ) 8.5
Hz, 1H), 7.31 (s, 2H), 7.27 (d, J ) 7.9 Hz, 1H), 7.21-7.17 (m,
3H), 7.10 (d, J ) 7.5 Hz, 1H), 7.05 (d, J ) 7.9 Hz, 2H), 4.92 (s,
2H), 4.53 (s, 2H), 1.18 (s, 9H), 0.84 (s, 9H), -0.04 (s, 6H); 13C
NMR (100 MHz, DMSO-d6) δ 166.69, 164.82, 149.11, 142.39,
142.10, 134.97, 133.79, 132.39, 131.99, 131.54, 130.00, 128.72,
126.81, 125.79, 124.89, 124.50, 123.67, 120.66, 63.73, 52.19,
34.04, 31.06, 25.77, 17.90, -5.35; HRMS-FAB (M + Na+) calcd
for C39H43BrN2O4SiNa 733.2073, found 733.2052.
2-Am in o-5-br om o-N-[[[(1,1-d im eth yleth yl)d im eth ylsi-
lyl]oxy]m eth yl]ph en yl]-N-[[4-(1,1-dim eth yleth yl)ph en yl]-
m et h yl]b en za m id e (15). A 250-mL round-bottomed flask
was charged with 2.80 g (3.93 mmol) of compound 14, 0.20 g
(0.2 mL, 6.30 mmol) of hydrazine, and 100 mL of methanol.
The solution was stirred and heated at reflux for 6 h under a
nitrogen atmosphere. The solution was then cooled and concd
in vacuo. The residue was mixed with 200 mL of ethyl acetate
and 200 mL of toluene and stirred for 15 h at room temper-
ature. The precipitated residue was filtered off, mixed again
with 100 mL of 1:1 ethyl acetate/toluene, and stirred for 4 h
at room temperature. After filtration the combined filtrates
were washed twice with 200-mL portions of water and once
with 200 mL of brine and dried over MgSO4. The solvent was
removed by rotary evaporation, and 2.28 g (3.92 mmol, 100%)
of the product was obtained as a white foam: Rf 0.25 (25:75
ethyl acetate/hexanes); 1H NMR (400 MHz, CDCl3) δ 7.33-
7.23 (m, 4H), 7.13-6.98 (m, 4H), 6.88 (m, 2H), 6.54 (d, J ) 8.4
Hz, 1H), 5.06 (s, 2H), 4.59 (s, 2H), 1.30 (s, 9H), 0.92 (s, 9H),
0.02 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 169.29, 150.26,
145.09, 143.40, 143.02, 134.27, 133.18, 132.11, 128.93, 127.77,
125.55, 125.50, 124.55, 124.33, 121.84, 118.42, 108.69, 64.30,
53.39, 34.52, 31.39, 25.98, 18.39, -5.22; HRMS-FAB (M + Na+)
calcd for C31H41BrN2O2SiNa 603.2018, found 603.1989. Anal.
Calcd for C31H41BrN2O2Si: C, 64.01; H, 7.10; N, 4.82. Found:
C, 64.30; H, 7.22; N, 4.78.
DMSO-d6) δ 168.58, 166.79, 166.67, 164.29, 149.26, 142.05,
141.92, 135.04, 134.03, 132.25, 128.44, 127.07, 125.68, 125.00,
124.49, 124.24, 63.44, 52.33, 34.05, 31.04, 25.65, 17.76, -5.48;
HRMS-FAB (M + Na+) calcd for C34H42BrClN6O2SiNa 731.1909,
found 731.1916.
2-[(4-Am in o-6-[(3,3-d im eth ylbu tyl)a m in o]-1,3,5-tr ia zin -
2-yl)a m in o]-5-br om o-N-[3-[[[(1,1-d im eth yleth yl)d im eth -
ylsilyl]oxy]m e t h yl]p h e n yl]-N -[[4-(1,1-d im e t h yle t h yl)-
p h en yl]m eth yl]ben za m id e (17). A solution of compound 16
(1.79 g, 2.52 mmol), neohexylamine (1.10 g, 10.87 mmol), and
diisopropylethylamine (0.87 g, 6.73 mmol) in THF (150 mL)
was heated at reflux for 10 h under an atmosphere of N2. The
reaction mixture was then cooled and concd in vacuo. The
residue was mixed with EtOAc (150 mL), washed with H2O
(2 × 150 mL) and brine (150 mL), dried over MgSO4, filtered,
and concd in vacuo. The mixture was purified by column
chromatography (eluted with 50:50 EtOAc/hexanes) to give
1.94 g (2.50 mmol, 99%) of the product as a white-foam solid:
Rf 0.20 (50:50 EtOAc/hexanes); 1H NMR (500 MHz, DMSO-
d6) δ 8.44-8.35 (m, 2H), 7.28 (d, J ) 6.2 Hz, 2H), 7.23-7.16
(m, 4H), 7.11-7.01 (m, 3H), 6.87 (s, 2H), 6.52 (s, 1H), 6.40 (s,
1H), 5.04 (s, 2H), 4.47 (s, 2H), 3.26 (bs, 2H), 1.43 (bs, 2H), 1.22
(s, 9H), 0.90 (s, 9H), 0.78-0.77 (two conformers, s, 9H), -0.11,
-0.12 (two conformers, 6H); 13C NMR (125 MHz, DMSO-d6) δ
167.87, 165.87, 149.37, 142.31, 137.99, 133.85, 132.10, 130.90,
128.73, 127.20, 125.09, 124.32, 111.59, 63.24, 52.42, 43.07,
42.71, 36.44, 34.06, 31.01, 29.28, 25.60, 17.70, -5.54; HRMS-
FAB (M + Na+) calcd for C40H56BrN7O2SiNa 796.3346, found
796.3370.
2-[(4-Am in o-6-[(3,3-d im eth ylbu tyl)a m in o]-1,3,5-tr ia zin -
2-yl)a m in o]-5-b r om o-N-[[4-(1,1-d im et h ylet h yl)p h en yl]-
m eth yl]-N-[3-(h yd r oxym eth yl)p h en yl]ben za m id e (18). A
solution of HOAc (45 mL) and H2O (15 mL) was added
dropwise to a solution of compound 17 (0.80 g, 1.03 mmol) in
THF (15 mL) at 0 °C under an atmosphere of N2. The reaction
mixture was warmed to room temperature and stirred for 3
days. This solution was concd in vacuo, and the residue was
partitioned between toluene (200 mL) and H2O (100 mL). The
organic extract was washed with H2O (2 × 150 mL) and brine
(100 mL), dried over MgSO4, filtered, and concd in vacuo. The
residue was purified by column chromatography (eluted with
EtOAc) to give 0.57 g (0.86 mmol, 84%) of the product as a
1
white solid: Rf 0.28 (EtOAc); H NMR (400 MHz, DMSO-d6)
δ 8.47-8.38 (two conformers, bs, 1H), 8.27 (m, 1H), 7.32-7.30
(m, 3H), 7.20-7.10 (m, 6H), 7.01-6.85 (m, 2H), 6.66-6.57 (two
conformers, bs, 2H), 5.20 (s, 1H), 5.05 (s, 2H), 4.34 (s, 2H),
3.26 (bs, 2H), 1.46-1.35 (m, 2H), 1.24 (s, 9H), 0.92, 0.90 (two
conformers, s, 9H); 13C NMR (125 MHz, DMSO-d6) δ 167.69,
165.03, 149.41, 143.73, 142.06, 141.85, 133.94, 132.20, 131.71,
130.98, 128.56, 127.17, 125.44, 125.10, 124.72, 124.50, 62.14,
52.49, 42.96, 42.63, 36.61, 34.09, 31.06, 29.32; HRMS-FAB (M
+ Na+) calcd for C34H42BrN7O2Na 682.2481, found 682.2490.
Anal. Calcd for C34H42BrN7O2: C, 61.81; H, 6.41; N,14.84.
Found: C, 61.90; H, 6.64; N, 14.61.
2-[(4-Am in o-6-[(3,3-d im eth ylbu tyl)a m in o]-1,3,5-tr ia zin -
2-yl)a m in o]-5-br om o-N-[3-(br om om eth yl)p h en yl]-N-[[4-
(1,1-d im eth yleth yl)p h en yl]m eth yl]ben za m id e (19). A so-
lution of PBr3 (0.162 g, 56.8 µL, 0.60 mmol) and pyridine (0.10
mL, 0.098 g, 1.24 mmol) in THF (1 mL) was added slowly to
a solution of compound 18 (0.60 g, 0.91 mmol) and pyridine
(0.1 mL, 0.098 g, 1.24 mmol) in THF (80 mL) at 0 °C under an
atmosphere of N2 via syringe. The addition was complete in
30 min. After an additional 1 h, the reaction mixture was
warmed to room temperature and concd in vacuo. The residue
was partitioned between EtOAc (100 mL) and saturated
NaHCO3 solution (30 mL). The organic extract was washed
with H2O (100 mL), brine (100 mL) and dried over MgSO4,
filtered, and concd in vacuo. The residue was purified by
column chromatography (eluted with 50:50 EtOAc/hexanes)
to give 0.61 g (0.84 mmol, 92%) of the product as a white
solid: Rf 0.24 (50:50 EtOAc/hexanes); 1H NMR (500 MHz,
CDCl3) δ 8.41 (bs, 1H), 8.17, 8.04 (two conformers, bs, 1H),
7.33-7.20 (m, 4H), 7.13-7.05 (m, 4H), 6.89 (s, 1H), 6.82 (d, J
) 6.5 Hz, 2H), 5.24, 5.13 (two conformers, bs, 2H), 5.05 (s, 2H),
4.24 (s, 2H), 3.39 (m, 2H), 1.46 (m, 2H), 1.30 (s, 9H), 0.96 (s,
9H); 13C NMR (125 MHz, CDCl3) δ 168.52, 165.39, 164.47,
150.67, 142.92, 139.12, 136.87, 133.76, 132.66, 131.43, 129.53,
2-[(4-Am in o-6-ch lor o-1,3,5-tr iazin -2-yl)am in o]-5-br om o-
N-[3-[[[(1,1-d im et h ylet h yl)d im et h ylsilyl]oxy]m et h yl]-
p h e n yl]-N -[[4-(1,1-d im e t h yle t h yl)p h e n yl]m e t h yl]b e n -
za m id e (16). A solution of amine 15 (2.00 g, 3.44 mmol),
cyanuric chloride (1.00 g, 5.42 mmol), and diisopropylethyl-
amine (1.33 g, 10.3 mmol) in THF (100 mL) was stirred under
o
N2 at 0 C for 1.5 h, and then gaseous ammonia was passed
through the solution for an additional 1.5 h. The solution was
then warmed to room temperature, and the solvent was
removed in vacuo. The residue was partitioned between ethyl
acetate/toluene (1:1) (400 mL) and water (100 mL). The
organic extract was washed with H2O (2 × 100 mL) and brine
(50 mL), dried over MgSO4, filtered, and concd in vacuo. The
mixture was purified by column chromatography (eluted with
33:66 EtOAc/hexanes) to give 2.05 g (2.89 mmol, 84%) of the
1
product as a white solid: Rf 0.28 (33:66 EtOAc/hexanes); H
NMR (500 MHz, DMSO-d6) δ 9.38 (s, 1H), 7.62 (s, 1H), 7.60
(s, 1H), 7.45-7.41 (m, 2H), 7.28-7.26 (m, 3H), 7.16-7.14 (m,
2H), 7.11-7.07 (m, 3H), 7.00 (s, 1H), 5.00 (s, 2H), 4.47 (s, 2H),
1.23 (s, 9H), 0.80 (s, 9H), -0.08 (s, 6H); 13C NMR (125 MHz,