Chemistry Reference
In-Depth Information
Work-up, Method B: The solvent (dichloromethane) was completely removed, and
the residue was extracted several times with small amounts of eluent (for example,
hexane/ethyl acetate, 4:1). The resulting suspension was subjected to silica gel
chromatography at between
30
C.
45 and
Typical procedure. Mesityl isocyanate 349 using a catalytic amount of DMAP and Boc
2
O
[221]:
A solution of Boc
2
O (619 mg, 2.84 mmol) in acetonitrile (2 mL) was treated
successively with a solution of 4-dimethylaminopyridine (33 mg, 0.27 mmol) in
acetonitrile (2 mL) and a solution of 348 (365 mg, 2.7 mmol) in acetonitrile (2 mL).
The reaction mixture was stirred vigorously for 10 min. After the addition of con-
centrated sulfuric acid in acetonitrile (40% solution, r ¼
03 g cm
3
, 0.47 mL), the
resulting mixture was stirred for 5 min. Water (0.47 mL) was then added, and the
mixture was stirred for a further 5 min. The reaction mixture was then poured into
an equal volume of water. The solution was extracted three times with hexane, and
the combined hexane layers were dried over magnesium sulfate. Removal of the
solvent in vacuo afforded mesityl isocyanate 349 (420 mg, 97%) as colorless crystals;
mp 42
C.
1
:
Other activated carbonates Efforts have been made to accomplish the isocyanation
of amines with C
1
building blocks that, unlike Boc
2
O, can be synthesized without
the use of phosgene.
O
O
1.0 equiv DMAP
CH
3
CN
ArNH
2
NCO
Ar
R
1
O
2
ArHN
NHAr
348
350
349
351
Ar = Mesityl
In fact, other activated carbonates 350 can be used for the isocyanation of amines
in the presence of DMAP (Table 4.16). However, due to its extreme reactivity,
Boc
2
O provides the highest yields in a very rapid reaction. As an alternative to
Boc
2
O, tert-butoxycarbonyl pivalate 350b has been synthesized, which is readily
Tab. 4.16.
DMAP-mediated synthesis of mesityl isocyanate (349) from mesitylamine 348 with
the activated carbonates 350 as C
1
building blocks (350a ¼ Boc
2
O) [221].
R
1
R
2
350
T (˚C)
t
349 yield
(%)
351 yield
(%)
a
tBuOCO
tBu
25
10 min
96
0
b
tBuCO
tBu
25
4 h
17
64
c
C
6
H
5
C
6
H
5
82
15 d
0
29
d
4-O
2
NC
6
H
4
4-O
2
NC
6
H
4
25
18 h
19
64
e
4-O
2
NC
6
H
4
4-O
2
NC
6
H
4
82
18 h
9
86
