Chemistry Reference
In-Depth Information
Typical procedure. 2-Isocyanatoacetyl chloride 1231 from glycine and phosgene [447]:
Phosgene (for safe phosgenation, see Chapter 7) was passed in a fine stream into a
suspension of finely ground glycine (25 g) in dry dioxane (750 mL) at 45-50
C
with stirring. After 6 h, the mixture had become almost clear. The reaction was
allowed to proceed for a further 3 h. The solution obtained was then filtered to
remove a small amount of insoluble solid and concentrated under reduced pres-
sure at a temperature below 50
C. The residue, consisting of white crystals and
a violet oil, was filtered with the aid of diethyl ether (50 mL). The crystals of 2,5-
oxazolidinedione 1228 were collected, washed with dry diethyl ether, and dried over
P
2
O
5
in a vacuum desiccator. They weighed 5.5 g (16%). The filtrate was distilled to
yield 12 g (30%) of an irritating colorless liquid, 2-isocyanatoacetyl chloride, 1231.
Other 2-isocyanatoacyl chlorides have also been prepared from the correspond-
ing a-amino acids and phosgene by a similar procedure to that described above.
Typical procedure. 2-Isocyanatoacetyl chloride 1231 from 2,5-oxazolidinedione, hydrogen
chloride, and phosgene [447]: Into a solution of 2,5-oxazolidinedione 1228 (10 g)
in dry dioxane (300 mL), phosgene (for safe phosgenation, see Chapter 7) and then
hydrogen chloride were passed at 10
C with stirring for 1 h each. The solution was
then maintained at 50
C and treated with phosgene for 7 h. After 2 days, the so-
lution was concentrated under reduced pressure, and the residual brown liquid
was distilled to yield 10.5 g (89.0%) of 2-isocyanatoacetyl chloride, bp 54.5-56.5
C
(22 mmHg).
Trichloroacetyl chloride in dioxane [859] and nitrogen monoxide in DMSO [906]
have also been reported as reagents for the preparation of NCAs.
4.3.5.5
N,COOH Binucleophiles. Synthesis of 1H-Benzo[d ][1,3]oxazine-2,4-diones
(Isatoic Anhydrides)
1H-Benzo[d][1,3]oxazine-2,4-diones (isatoic anhydrides) have long been prepared
from anthranilic acids 1232 using ethyl chloroformate [907, 908], acetyl chloride
[909, 910], PhSO
2
Cl and pyridine [911], morpholine- or pyrrolidine-urea deriva-
tives [912], and diphosgene [161, 913].
O
O
Phosgene
or
Phosgene Equiv
OH
O
R
R
NH
2
N
H
O
1232
1233
Under practically the same experimental conditions as those used to prepare NCAs
of amino acids, phosphorus tribromide reacts with N-carbobenzoxyanthranilic acid
to give nearly quantitative yields of isatoic anhydride [858].
Typical procedure. Isatoic anhydride [858]:
Phosphorus tribromide (0.035 mol) was
added to a solution of N-carbethoxy- or N-carbobenzoxy-anthranilic acid (0.1 mol;
