Chemistry Reference
In-Depth Information
prepared by coupling anthranilic acid with the corresponding carbalkoxy chloride
in the usual way) in anhydrous diethyl ether (100 mL). After 24 h at room tem-
perature, isatoic anhydride had separated as a microcrystalline product. It was col-
lected by filtration, washed with dry diethyl ether, and recrystallized from ethanol.
Yield ca. 90%.
Isatoic anhydrides 1235 were prepared from the corresponding anthranilic acids
with triphosgene [914].
Br
O
Br
O
R
R
(CCl
3
O)
2
CO
O
OH
N
H
O
NH
2
1234
1235
Br
Br
O
O
R
R
O
+
RCOOOH
O
N
H
N
H
1237
O
R = Me, Cl
1235
1236
R = Me, MeO, Et, Cl
Attempts to synthesize isatoic anhydride 1235 directly from isatin 1236 by peracid
oxidation with 1237 were unsuccessful.
Typical procedure. 5-Bromo-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione 1235 (R ¼ Me)
[914]:
Under anhydrous conditions, 6-bromo-5-methylanthranilic acid (2.3 g, 10
mmol) was stirred with triphosgene (1.0 g, 3.4 mmol) in THF (25 mL) for 12 h.
The resultant solid was collected by filtration, washed with cold acetone, and dried
in vacuo. Isatoic anhydride was isolated in quantitative yield and used without fur-
ther purification.
5-Bromo-6-chloro-1H-benzo[d][1,3]oxazine-2,4-dione was prepared by reacting
anthranilic acid and triphosgene as described above; yield 72% [914].
Cyclization of N-substituted anthranilic acids using triphosgene, diphosgene,or
chloroformates has been claimed in patent literature [915]. For example 2-N-cyclo-
propylamino-4,5-difluorobenzoic acid 1238 was converted into N-cyclopropyl-6,7-
difluoro-2H-1,3-benzoxazine-2,4(1H)-dione 1239 in quantitative yield.
O
O
F
F
(CCl
3
O)
2
CO
OH
O
Et
3
N, CH
2
Cl
2
,DMAP,
0 °C, 1.5 h
F
NH
F
N
O
1238
1239
