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
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.
1
4. 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
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