Organic Syntheses, Coll. Vol. 3, p.392 (1955); Vol. 24, p.56 (1944).
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.
) (Note 4)
and (Note 5)
layer should be removed as rapidly as possible from the aqueous layer, because ethyl diazoacetate
is rapidly decomposed by acid.
may be purified, but with considerable loss, by steam distillation under reduced pressure.1
The submitters have carried out preparations using twice the amounts stated.
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.
This preparation is referenced from:
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