Chemistry Reference
In-Depth Information
Phosgenation of O-benzylhydroxylamine 158 with phosgene did not allow the iso-
lation of the desired carbamoyl chloride or the corresponding N-benzyloxyurea.
More complex transformations occurred depending on the catalyst and conditions.
McKay isolated the 1,3,5-tribenzyloxyisocyanuric acid 159 when triethylamine was
added to a solution of benzylhydroxylamine hydrochloride and phosgene in chloro-
benzene that had been heated at reflux [100].
OBn
1.
COCl
2
O
N
O
NH
2
PhCl, 125°C
O
NN
2. Et
3
N
BnO
OBn
O
158
159
N
N
Cl
1.
COCl
2
, PhCl, 125°C
O
O
2. 3,4-dichloroaniline
Cl
Cl
160
In the absence of triethylamine, heating benzylhydroxylamine with phosgene
under the same conditions, followed by the addition of 3,4-dichloroaniline, gave
trichloride 160; chlorination had occurred under the reaction conditions. Further-
more, it was also found that the reactive intermediate in this process was neither
an alkoxy isocyanate nor a chloroformate, but rather the allophanate 161.
N
N
O
O
O
O
161
The preparation of N-benzyloxyureas without phosgene can be accomplished using
several coupling agents, including 2(S),3-pyridinediyl thiocarbonate (PTC) [101],
N,N
-carbonyldiimidazole (CDI) [102, 103], triphosgene, (p-nitrophenoxy)carbonyl
chloride [104], and ethyl chloroformate [105] (see also Section 4.3 on carbony-
lation). Experimental studies revealed the imidazolylcarbonyl synthon 162 to be a
superior synthetic equivalent [106].
O
H
NN
N
O
O
162
Treating O-benzylhydroxylamine 158, as the free base, with triphosgene under
nitrogen in dioxane at 100
C, followed by cannulation of this solution into a mix-
