A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1945, 25, 46
DOI: 10.15227/orgsyn.025.0046
[2-Pentenoic acid, 2-cyano-3-ethyl-, ethyl ester]
Submitted by Arthur C. Cope and Evelyn M. Hancock.
Checked by H. R. Snyder and J. H. Saunders.
1. Procedure
In a 500-ml. round-bottomed flask attached to a modified Dean and Stark constant water separator1 (Note 1) which is connected to a reflux condenser are placed 67.8 g. (0.60 mole) of ethyl cyanoacetate (Note 2), 56.8 g. (0.66 mole) of diethyl ketone (Note 3), 9.2 g. (0.12 mole) of ammonium acetate, 30 g. (0.48 mole) of glacial acetic acid, and 100 ml. of benzene. The flask is heated in an oil bath at 160–165°, and the water that distils out of the mixture with the refluxing benzene is removed from the separator at intervals. Refluxing is continued for 24 hours (several hours after the separation of water has ceased) (Note 4).
The solution is cooled and washed with three 25-ml. portions of 10% sodium chloride solution, after which the benzene is removed by distillation under reduced pressure. The residue is transferred to a 1-l. bottle, a solution of 78 g. (0.75 mole) of commercial sodium bisulfite in 310 ml. of water is added, and the mixture is shaken on a mechanical shaker for 2 hours. The turbid solution is diluted with 500 ml. of water and extracted with three 50-ml. portions of benzene. The extracts are discarded (Note 5). The bisulfite solution is then cooled in an ice bath, and an ice-cold solution of 32 g. (0.8 mole) of sodium hydroxide in 130 ml. of water is added dropwise with mechanical stirring. The ester which separates is extracted at once with four 25-ml. portions of benzene (Note 6). The benzene solution is washed with 50 ml. of 1% hydrochloric acid, dried for a short time over 20 g. of anhydrous sodium sulfate, filtered into a 250-ml. modified Claisen flask, and distilled under reduced pressure. The yield of ester boiling at 123–125°/12 mm. (Note 7) is 65.4–75 g. (60.5–68%) (Note 8), (Note 9), and (Note 10).
2. Notes
1. Any continuous water separator that will return the benzene to the reaction mixture may be used.
2. Commercial ethyl cyanoacetate (Dow Chemical Company) was redistilled before use; b.p. 93–94°/12 mm.
3. Diethyl ketone was either purchased from the Eastman Kodak Company and redistilled, or prepared by passing propionic acid slowly over a mixture of manganous oxide and clay plate chips in a tube furnace at 420–440°;2 the apparatus was similar to one described in Organic Syntheses.3 When prepared by this method the ketone was distilled, dried over potassium carbonate, and redistilled; b.p. 100–101°.
4. The water layer (20–25 ml.) contains some acetic acid and acetamide, the acetamide being formed from the ammonium acetate catalyst.
5. Extraction of the aqueous solution removes ethyl cyanoacetate from the aqueous solution of the sodium bisulfite addition product of ethyl (1-ethylpropylidene)cyanoacetate.
6. The unsaturated ester is regenerated when the bisulfite is neutralized with sodium hydroxide. The solution is kept cold during neutralization and extraction, and but little excess sodium hydroxide is used in order to prevent hydrolytic cleavage of the ester to diethyl ketone and ethyl cyanoacetate.
7. Other boiling points are 135–137°/25 mm. and 88–89°/1 mm.
8. A number of ketones have been condensed with ethyl cyanoacetate by this procedure. Reactive ketones such as aliphatic methyl ketones and cyclohexanone condense with ethyl cyanoacetate much more rapidly and give better yields of alkylidene esters. It is advantageous with such ketones to use a lower ratio of ammonium acetate-acetic acid catalyst.1
9. The sodium bisulfite purification step may be omitted, and the alkylidene ester purified directly by distillation. Care must be taken to separate the product from ethyl cyanoacetate by fractionation through a moderately efficient column. Purification through the bisulfite addition compound is recommended for alkylidene cyanoacetic esters derived from ketones containing four and five carbon atoms, but not for the higher homologs. The checkers obtained a slightly higher yield by the method employing fractional distillation (64% vs. 60.5%) but the quality of the product appeared to be slightly inferior (n25D 1.4645 vs. 1.4649).
10. A trace of a water-soluble white solid may cause the distillate to be slightly turbid. It may be removed by washing the product with water and redistilling.
3. Discussion
The above procedure is a very slight modification of a general method1 for condensing ketones with ethyl cyanoacetate. Ethyl (1-ethylpropylidene)cyanoacetate also has been prepared by condensing diethyl ketone with ethyl cyanoacetate in the presence of piperidine or acetic anhydride and zinc chloride,4 or piperidine and anhydrous sodium sulfate in a pressure bottle at 100°.5
This preparation is referenced from:

References and Notes
  1. Cope, Hofmann, Wyckoff, and Hardenbergh, J. Am. Chem. Soc., 63, 3452 (1941).
  2. Sabatier and Mailhe, Compt. rend., 158, 831 (1914).
  3. Org. Syntheses Coll. Vol. 2, 389 (1943).
  4. Birch and Kon, J. Chem. Soc., 1923, 2448.
  5. Cowan and Vogel, J. Chem. Soc., 1940, 1528.

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)


potassium carbonate (584-08-7)

hydrochloric acid (7647-01-0)

Acetamide (60-35-5)

acetic acid (64-19-7)

Benzene (71-43-2)

ammonium acetate (631-61-8)

acetic anhydride (108-24-7)

sodium hydroxide (1310-73-2)

Cyclohexanone (108-94-1)

sodium chloride (7647-14-5)

propionic acid (79-09-4)

sodium sulfate (7757-82-6)

sodium bisulfite (7631-90-5)

carbon (7782-42-5)

piperidine (110-89-4)

zinc chloride (7646-85-7)

Ethyl cyanoacetate (105-56-6)

manganous oxide

diethyl ketone (96-22-0)

Ethyl (1-ethylpropylidene)cyanoacetate,
2-Pentenoic acid, 2-cyano-3-ethyl-, ethyl ester (868-04-2)

ammonium acetate-acetic acid