Organic Syntheses, CV 4, 454
Submitted by Nathan Kornblum and Robert K. Blackwood
1.
Checked by James Cason, Joanne Facaros, and William G. Dauben.
1. Procedure
Ethyl α-bromobutyrate (58.5 g., 0.30 mole) (Note
1) is poured into a stirred mixture of
600 ml. of N,N-dimethylformamide (DMF) (Note
1),
36 g. of sodium nitrite (0.52 mole) (Note
1), and
40 g. of anhydrous phloroglucinol (0.32 mole) (Note
2) contained in a
1-l. three-necked flask equipped with a
sealed stirrer. The flask is closed, except for a
tube containing calcium chloride, and immersed in a
water bath maintained at room temperature (Note
3). Stirring is continued for 2.5 hours (Note
4); then the reaction mixture is poured into 1.2 l. of ice water layered over with
300 ml. of ether (Note
5). After separation of the upper layer, the aqueous phase is extracted with four
100-ml. portions of ether. The combined extracts are washed with four 100-ml. portions of water and then dried over anhydrous
magnesium sulfate. The
magnesium sulfate is removed by suction filtration and washed with four
25-ml. portions of ether which are combined with the filtered extract.
The
ether is distilled through a small column (Note
6), under reduced pressure, from a 1-l. flask which is heated by a bath whose temperature is gradually raised to about 60°. The residual yellow liquid is transferred, with the aid of a little anhydrous
ether, to a
100-ml. flask, and the remaining solvent is distilled through the column under reduced pressure. Rectification of the residue yields 2–3 g. of fore-run boiling in the range 33–71°/1 mm. which is followed by
33–36 g. (
68–75%) of colorless
ethyl α-nitrobutyrate, b.p.
71°/1 mm., n
D20 1.4233 (Note
7), (Note
8), and (Note
9).
2. Notes
1. The
ethyl α-bromobutyrate employed was redistilled Eastman Kodak white label grade material, b.p.
64°/15 mm.,
nD 1.4479.
Technical DMF (du Pont) was used, and the
sodium nitrite was an analytical grade.
Subsequent to the checking of this preparation, the submitters reported that
DMSO (dimethyl sulfoxide) may be a somewhat better solvent for this preparation than is
DMF. Since
sodium nitrite is more soluble in
DMSO, only 250 ml. of this solvent is required for the preparation. The more concentrated solution permits a reduction in reaction time to about 1.5 hours.
2.
Ringwood Chemical Corporation technical grade phloroglucinol dihydrate was rendered anhydrous by heating for 3 hours at 110°. By reacting rapidly with any
ethyl α-nitritobutyrate formed, it prevents nitrosation of the α-nitro ester. In the absence of
phloroglucinol all the
ethyl α-nitrobutyrate is destroyed.
2,3
3. The reaction mixture becomes homogeneous and turns deep redbrown shortly after the addition of the α-bromo ester. The deep color is, presumably, due to nitrosated
phloroglucinol; however, this in no way interferes with subsequent isolation of product.
4. Two hours allows more than sufficient time for complete reaction. Since the yield is not critically dependent on this factor, no attempt was made to establish the minimum reaction time. Even after a 17-hour reaction time there is no decrease in yield.
5. Approximately 200 ml. of this ether is required to saturate the aqueous
DMF layer.
6. A
60 × 1 cm. externally heated column, packed with 1/8-in. glass helices and equipped with a total reflux variable take-off head, was used by the submitters.
7. Toward the end of the rectification the jacket of the column is heated to 90–95° in order to obtain the last few grams of product.
9. This procedure has been applied successfully to the synthesis of other α-nitro esters from α-bromo esters,
3 as listed below;
ethyl bromoacetate is exceptional in that it fails to give
ethyl nitroacetate.
3. Discussion
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved