Organic Syntheses, CV 5, 373
Submitted by Arthur J. Zambito and Eugene E. Howe
1.
Checked by John C. Sheehan and Alma M. Boston.
1. Procedure
A.
Diethyl isonitrosomalonate. In a
500-ml. three-necked, round-bottomed flask, equipped with a
mechanical stirrer and
thermometer, is placed
50 g. (47.4 ml., 0.312 mole) of diethyl malonate. The flask is cooled in an
ice bath, and a mixture of
57 ml. of glacial acetic acid and 81 ml. of water is added with stirring. With the temperature at about 5°, a total of
65 g. of sodium nitrite (Note 1) (0.944 mole) is added in portions over a period of 1.5 hours, the temperature being maintained around 5° during the addition. After all the
sodium nitrite is added, the ice bath is removed, and the stirring is continued for 4 hours (Note
2). During this time, the temperature reaches a maximum of 34–38° within 2 hours and falls to about 29° by the end of the stirring period. Gases which escape during the reaction (mostly
oxides of nitrogen) are led to the
hood.
The reaction mixture is transferred to a
300-ml. separatory funnel and is extracted with two
50-ml. portions of ether. The combined ethereal solution of
diethyl isonitrosomalonate is used in the next step immediately or, if desired, may be used after storage in a refrigerator overnight (Note
3).
B.
Diethyl acetamidomalonate. The solution of
diethyl isonitrosomalonate described above,
86 g. (0.842 mole) of acetic anhydride, and
225 ml. (3.95 moles) of glacial acetic acid are placed in a
1-l., three-necked, round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a
dropping funnel. With vigorous stirring
78.5 g. (1.20 moles) of zinc dust is added in small portions over a period of 1.5 hours in such a manner that the temperature of the reaction is maintained at 40–50°. The reaction is markedly exothermic during most of the
zinc addition, and intermittent cooling (
water bath) is required. After all the metal has been added, the mixture is stirred for an additional 30 minutes.
The reaction mixture is filtered with suction and the cake is washed thoroughly with two
200-ml. portions of glacial acetic acid (Note
4). The combined filtrate and washings are evaporated under reduced pressure on the
steam bath until a thick oil, which generally partially crystallizes, remains. To purify the crude product, 100 ml. of water is added, and the flask is warmed on a steam bath until the solid melts. The mixture of water and oil is stirred rapidly in an ice bath, and
diethyl acetamidomalonate crystallizes as a fine white product. After cooling in an ice bath for an additional hour, the product is collected by filtration, washed once with cold water, and dried in air at 50°. A second crop is obtained by concentrating the mother liquor under reduced pressure. The yield of
diethyl acetamidomalonate, m.p.
95–97° (Note
5), is
52–53 g. (
77–78%) based on malonic ester.
2. Notes
1. Owing to the instability of
sodium nitrite solutions, the addition of the solid salt is preferred.
4. The
zinc cake is very heavy and may be washed by slurrying on a
sintered-glass funnel or, if a standard
Büchner funnel is used, by removing and slurrying in a
beaker.
5. The
diethyl acetamidomalonate obtained is of high purity. If a product of inferior quality is obtained, it may be recrystallized from hot water, using 2.5 cc. per g. Upon cooling, the product separates first as an oil. With rapid stirring, it is converted to fine white crystals which are easily washed with cold water.
Diethyl acetamidomalonate may be recrystallized in this manner with
97% recovery. The first crop amounts to
91% and the mother liquors may be concentrated to yield an additional
6%.
3. Discussion
This preparation is referenced from:
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved