A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1946, 26, 31
DOI: 10.15227/orgsyn.026.0031
[Caproic acid, α-cyano-, ethyl ester]
Submitted by Elliot R. Alexander and Arthur C. Cope.
Checked by Cliff S. Hamilton and Robert F. Coles.
1. Procedure
A mixture of ethyl cyanoacetate (Note 1) (56.6 g., 0.5 mole), freshly distilled butyraldehyde (43.2 g., 0.6 mole), 1 g. of palladium on carbon (Note 2), and 80 ml. of glacial acetic acid is placed in a 500-ml. bottle suitable for attachment to a low-pressure reduction apparatus. A solution of piperidine (2.0 ml., 0.02 mole) in 20 ml. of glacial acetic acid is added, and the bottle is connected to the reduction apparatus.
The bottle is alternately evacuated and filled with hydrogen twice, and the mixture is reduced by shaking with hydrogen at 1 to 2 atm. (15–30 lb.) pressure. The reduction is rapid and exothermic. In 1–2 hours the theoretical amount of hydrogen (0.5 mole) is taken up and absorption ceases (Note 3).
The reaction mixture is filtered through a Hirsch or Büchner funnel, and the bottle is rinsed with 50 ml. of benzene, which is also poured through the funnel. The filtrate is washed with two 50-ml. portions of 10% sodium chloride solution and three 25-ml. portions of water (Note 4). The washings are extracted with three 10-ml. portions of benzene, and the combined benzene solutions are distilled under reduced pressure from a 250-ml. modified Claisen flask. The yield of ethyl n-butylcyanoacetate, b.p. 108–109°/9 mm., is 79–81 g. (94–96%, based on the ethyl cyanoacetate used) (Note 5).
2. Notes
1. Ethyl cyanoacetate was purchased from the Dow Chemical Company, Midland, Michigan, and redistilled before using.
2. The palladium on carbon catalyst was prepared by the following method, developed by Walter H. Hartung, School of Pharmacy, University of Maryland, Baltimore. Ten milliliters of a commercial palladium chloride solution containing 0.1 g. of palladium and approximately 0.05 g. of hydrogen chloride per milliliter (obtained from the J. Bishop Company, Malvern, Pennsylvania) is added to a solution of 27 g. of sodium acetate trihydrate in 100 ml. of water. Norit (9 g.) is added, and the mixture is hydrogenated until absorption ceases. The catalyst (10 g.) is filtered on a Büchner funnel, washed with water, dried by drawing air through the funnel for about 30 minutes, and stored in a desiccator over calcium chloride. The palladium catalysts, prepared as described elsewhere in this volume, are presumably also satisfactory for the reductive alkylation described above (p. 685).
3. It is advisable to start the reduction as soon as the reactants are mixed. The yield dropped to 87% when the reaction mixture was allowed to stand for 3 hours before hydrogenating.
4. If an emulsion is formed, it can be broken by adding a few drops of ethanol or several milliliters of ether.
5. Ethyl ethylcyanoacetate and ethyl propylcyanoacetate have been prepared by the same method in yields of 85 and 94%, respectively. Other aldehydes and ketones have been used under slightly different conditions to prepare other ethyl monoalkylcyanoacetates.1
3. Discussion
Ethyl n-butylcyanoacetate has been prepared by alkylation of the sodium enolate of ethyl cyanoacetate with butyl bromide 2 and by condensation of capronitrile with ethyl carbonate,3 in addition to the method given above.1
This preparation is referenced from:

References and Notes
  1. Alexander and Cope, J. Am. Chem. Soc., 66, 886 (1944).
  2. Hessler and Henderson, J. Am. Chem. Soc., 43, 674 (1921).
  3. Wallingford, Jones, and Homeyer, J. Am. Chem. Soc., 64, 577 (1942).

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

sodium enolate of ethyl cyanoacetate

ethanol (64-17-5)

calcium chloride (10043-52-4)

hydrogen chloride (7647-01-0)

acetic acid (64-19-7)

Benzene (71-43-2)

ether (60-29-7)

hydrogen (1333-74-0)

sodium chloride (7647-14-5)

Butyl bromide (109-65-9)

Norit (7782-42-5)

piperidine (110-89-4)

palladium (7440-05-3)

butyraldehyde (123-72-8)

Ethyl cyanoacetate (105-56-6)

palladium chloride (7647-10-1)

ethyl carbonate

Caproic acid, α-cyano-, ethyl ester,

sodium acetate trihydrate (6131-90-4)

Ethyl ethylcyanoacetate

ethyl propylcyanoacetate

capronitrile (628-73-9)