Chemistry Reference
In-Depth Information
one-pot reaction with the first amine to produce the carbamoylbenzotriazole inter-
mediate 1022, which, under more forceful conditions, can react with a second
amine to give the final urea in satisfactory to good yields (24-85%) [728].
O
O
R
3
R
4
NH
Bt
2
CO
R
1
NN
R
3
R
1
R
2
NH
R
1
NN
- BtH
- BtH
R
2
R
4
R
2
NN
1022
1023
(25-85 %)
The reaction conditions and the yields of intermediate 1022 are significantly af-
fected by the steric hindrance of the substituents of the amines utilized. With cy-
clic, aliphatic, and aromatic amines, the reaction occurs within 2 days in THF at
room temperature in 40-71% yield, whereas with congested secondary amines
harsher conditions are required and lower yields are obtained. In laboratory-scale
preparations, N,N
-carbonyldibenzotriazole is synthesized directly from benzo-
triazole and phosgene.
O
Typical procedure. N-Phenyl-N
0
-n-octyl-urea [728]:
-Carbonyldibenzotriazole (1.06
g, 4 mmol) was dissolved in dry THF (40 mL) under an atmosphere of dry nitro-
gen, and aniline (0.37 mL, 4 mmol) was added. The reaction mixture was stirred at
room temperature for 27 h, octylamine (0.65 mL, 4 mmol) was then added, and the
resulting mixture was stirred at room temperature for 27 h. It was then extracted
1,1
O
Tab. 4.28.
Preparation of ureas by successive treatments of N,N
O
-carbonyldibenzotriazole with
R
1
R
2
NH and R
3
R
4
NH.
R
1
R
2
R
3
R
4
Product
1023
Yield (%)
a
Ph
H
n-octyl
H
85
a
b
Ph
H
-(CH
2
)O(CH
2
)
2
-
16
a
b
Ph
H
-(CH
2
)O(CH
2
)
2
-
70
b
c
n-Bu
Me
-(CH
2
)
4
-
82
c,d
d
n-Bu
Me
Ph
Me
80
c,d
e
n-Bu
Me
Ph
Me
71
c,d
f
-(CH
2
)O(CH
2
)
2
-
-(CH
2
)
3
-
71
c,d
g
-(CH
2
)O(CH
2
)
2
-
n-Bu
Me
80
c,d
h
-(CH
2
)O(CH
2
)
2
-
Benzyl
Me
25
c,d
i
-(CH
2
)O(CH
2
)
2
-
Ph
Ph
51
c,d
j
-(CH
2
)O(CH
2
)
2
-
Ph
Me
57
c,d
k
-(CH
2
)
2
N(CH
3
)(CH
2
)
2
-
Ph
Ph
47
c,d
l
-(CH
2
)
2
N(CH
3
)(CH
2
)
2
-
Ph
Me
51
c,d
a
One-pot procedure carried out at room temperature;
b
One-pot
procedure carried out at room temperature after addition of the
primary amine and with heating under reflux after addition of the
secondary amine;
c
Two-pot procedure;
d
Heating under reflux and use
of the sodium salt of the amine.
