Organic Syntheses, CV 1, 254
Submitted by J. K. H. Inglis
Checked by C. S. Marvel, W. F. Tuley, and S. V. Puntambeker.
1. Procedure
In a
5-l. round-bottomed flask,
500 g. (5.3 moles) of chloroacetic acid is dissolved in 700 cc. of water. The solution is warmed to 50° and neutralized with anhydrous
sodium carbonate of which about 290 g. (2.7 moles) is required (a slight excess of sodium carbonate is not disadvantageous). Meanwhile
294 g. (5.8 moles) of sodium cyanide (97 per cent) is dissolved in 750 cc. of water warmed to 55°. The
sodium cyanide solution is then added to the
sodium chloroacetate solution, which has been cooled to room temperature, with rapid mixing of the two solutions and cooling under the water tap. The temperature rapidly rises; when it reaches 95° the solution should be cooled by adding 200 cc. of cold water and this repeated, if necessary, until the temperature no longer rises (Note
1). The solution is heated to the boiling point and boiled for five minutes (Note
2), and finally cooled with running water for one-half hour.
The solution is filtered if not clear, and the
cyanoacetic acid is set free (
Hood) by adding with thorough stirring
694 g. (600 cc., 5.8 moles) (a slight excess) of commercial hydrochloric acid (sp. gr. 1.156). The solution is evaporated on a
water bath at 60–70° (Note
3) under a pressure of 20–30 mm. and the evaporation continued until practically no more distillate (Note
4) comes over. To the residue is added
600 cc. of 95 per cent alcohol. The solution is filtered (Note
5) from the
sodium chloride, and the residue is washed with another
500-cc. portion of alcohol.
On evaporating the alcoholic solution under reduced pressure from a water bath held at 50–60° (Note
6) the residue weighs about
540 g. A mixture of
600 cc. of absolute alcohol (p. 249) and
10 cc. of concentrated sulfuric acid (Note
7) is then added. The mixture is then heated on the water bath under a reflux condenser for three hours. The excess of alcohol and some of the water formed are removed by distillation under reduced pressure and the residue again heated for two hours with
300 cc. of absolute alcohol and an additional
4 cc. of concentrated sulfuric acid. The alcohol is removed by distillation under reduced pressure, and when the ester has cooled to room temperature, the
sulfuric acid is neutralized with a concentrated solution of
sodium carbonate; the ester (upper layer) is separated, and the aqueous solution extracted with
ether, or preferably
benzene; about one-tenth of the yield is in the extract. The combined products are placed in a
1-l. distilling flask and distilled under reduced pressure after the solvent and alcohol and water have been removed. The ester is collected at
94–99°, chiefly at
97–98°/16 mm. (Note
8). The yield of a product analyzing about
97–98 per cent
ethyl cyanoacetate amounts to
474–492 g. (
77–80 per cent of the theoretical amount) (Note
9) and (Note
10).
2. Notes
1. If the reaction between the cyanide and chloroacetate becomes too vigorous,
hydrogen cyanide is set free and partly changed to brown material and a corresponding amount of glycolate is formed.
2. The color at this stage should be yellow or a light brown.
3. If the mixture is heated to a higher temperature there is a considerable loss due to decomposition of the
cyanoacetic acid.
5. It is much easier to remove the salt by means of a
centrifuge. If this method is used the salt should be washed first with
500 cc. and then with 250 cc. of alcohol.
6. The solution containing mineral acid must not be evaporated at a high temperature or
diethyl malonate will be formed.
7. The addition of
sulfuric acid will probably produce a slight precipitate, but this may be ignored if the original treatment with
hydrochloric acid was properly carried out.
9. The product was analyzed for
nitrogen by the Kjeldahl method.
10. The procedure described in Org. Syn.
10, 48, for the esterification of
fumaric acid can probably be used for the preparation of the
methyl and the ethyl esters of cyanoacetic acid.
3. Discussion
This preparation is referenced from:
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