Org. Synth. 1944, 24, 56
DOI: 10.15227/orgsyn.024.0056
ETHYL DIAZOACETATE
[Acetic acid, diazo-, ethyl ester]
Submitted by Ennis B. Womack and A. B. Nelson.
Checked by R. L. Shriner and C. H. Tilford.
1. Procedure
A 1-l. three-necked round-bottomed flask is fitted with a 50-ml. separatory funnel and a mechanical stirrer sealed with a well-lubricated rubber collar. A stopper in the third neck of the flask carries a glass tube that reaches to the bottom of the flask, enters the top of a 1-l. separatory funnel, and extends down to the stopcock.
A solution of 140 g. (1 mole) of glycine ethyl ester hydrochloride and 3 g. of sodium acetate in 150 ml. of water is added to the flask and cooled to 2° by means of an ice-salt bath. A cold solution of 80 g. (1.15 moles) of sodium nitrite in 100 ml. of water is added, and the mixture is stirred until the temperature has fallen to 0°. The temperature is maintained below 2°, and stirring is continued throughout all the following operations. To the cold mixture are added 80 ml. of cold, ethanol-free ethyl ether (Note 1) and 3 ml. of cold 10% sulfuric acid. After 5 minutes, the reaction mixture is blown over into the 1-l. separatory funnel by application of air pressure. The lower aqueous layer is quickly sucked back into the reaction flask. The ether layer is removed and immediately washed with 50 ml. of cold 10% sodium carbonate solution. This ether solution should be neutral to moist litmus paper; if not, the washing with sodium carbonate is repeated. The ether solution is finally dried over 10 g. of anhydrous sodium sulfate.
A second portion of 80 ml. of ethanol-free ether is then added to the reaction mixture with stirring, followed by 15 ml. of cold 10% sulfuric acid over a period of 5 minutes. After 3 minutes' contact (Note 2), the ether layer is removed as before, washed immediately with 50 ml. of fresh 10% sodium carbonate solution, and dried over 10 g. of sodium sulfate. This procedure is repeated (about 6 or 7 times) until the ether layer is no longer yellow.
The combined ether solutions are then subjected to distillation at 20°or below under the vacuum obtainable from a water pump until all the ether is removed. Prolonged distillation results in decomposition of the diazo ester and in a decreased yield. The yellow residual oil is practically pure ethyl diazoacetate and is satisfactory for most synthetic purposes (Note 3). The yield is about 98 g. (85%) (Note 4) and (Note 5).
2. Notes
1.
The
ethanol is removed from
600 ml. of commercial ethyl ether by thorough washing with
75 ml. of a saturated calcium chloride solution.
2.
The
ether layer should be removed as rapidly as possible from the aqueous layer, because
ethyl diazoacetate is rapidly decomposed by acid.
3.
Ethyl diazoacetate may be purified, but with considerable loss, by steam distillation under reduced pressure.
14.
The submitters have carried out preparations using twice the amounts stated.
5.
The product should be placed in
dark brown bottles and kept in a cool place. It should be used as soon as possible.
Distillation, even under reduced pressure, is dangerous, for the substance is explosive.
3. Discussion
Ethyl diazoacetate has been prepared by the action of
sodium nitrite on
glycine ethyl ester hydrochloride.
1,2,3 A modification of this method, which is reported to give better yields than those described here, has been published.
4
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
ethanol (64-17-5)
calcium chloride (10043-52-4)
sulfuric acid (7664-93-9)
ether,
ethyl ether (60-29-7)
sodium acetate (127-09-3)
sodium carbonate (497-19-8)
sodium sulfate (7757-82-6)
sodium nitrite (7632-00-0)
ethyl diazoacetate,
Acetic acid, diazo-, ethyl ester (623-73-4)
Glycine ethyl ester hydrochloride (623-33-6)
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