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Org. Synth. 1950, 30, 80
DOI: 10.15227/orgsyn.030.0080
α-PHENYL-α-CARBETHOXYGLUTARONITRILE
[Butyric acid, 2,4-dicyano-2-phenyl-, ethyl ester]
Submitted by E. C. Horning and A. F. Finelli1.
Checked by William S. Johnson and H. Wynberg.
1. Procedure
In a 500-ml. three-necked flask equipped with a stirrer, a dropping funnel, and a thermometer is placed a solution of 57.0 g. (0.30 mole) of ethyl phenylcyanoacetate (p. 461) in 80 ml. of tert-butyl alcohol. The solution is heated to 40°, and with stirring the dropwise addition of a solution of 33.0 g. (0.62 mole) of acrylonitrile (Note 1) in 30 ml. of tert-butyl alcohol is started. After the addition of about 10–15 drops, 1.0 ml. of a 30% solution of potassium hydroxide in methanol is added, and the temperature is maintained at 40–45° by occasional external cooling while the remaining solution is added slowly. When about one-half of the acrylonitrile has been added, an additional 1.0 ml. of the potassium hydroxide solution is added to ensure the presence of a basic catalyst throughout the reaction. When the addition is completed (after about 30 minutes) and the temperature is no longer maintained above 40° by the exothermic reaction (another 30 minutes), the mixture is heated with a hot-water bath to keep the temperature at 40–45° for 1 hour.
The solution is diluted with 250 ml. of water and acidified with 30–40 ml. of 10% hydrochloric acid. The product is separated after the addition of 100 ml. of ether, and the aqueous solution is extracted with two 50-ml. portions of ether. The combined extracts are washed with 50 ml. of water and dried over anhydrous magnesium sulfate. The ether is distilled at atmospheric pressure, and the residue is distilled under reduced pressure through a short (15-cm.) Vigreux column. After a fore-run of a few grams, the product is collected at 157–167° /0.5–1 mm. (Note 2). The yield is 50–61 g. (69–83%).
2. Notes
1. The acrylonitrile should be distilled before use. Acrylonitrile vapors are toxic, and the distillation as well as the subsequent reaction should be carried out in a hood.
2. Other observed boiling points are 165–167° /1 mm., 195–200° /6 mm. The product is a colorless, viscous oil, n25D 1.5100–1.5103.
3. Discussion
α-Phenyl-α-carbethoxyglutaronitrile has been prepared by the reaction of ethyl α-cyanophenylacetate with β-chloropropionitrile in the presence of sodium amide.2 The present procedure has been published,3 and it follows the general method described by Bruson4 for the cyanoethylation of arylacetonitriles.
This preparation is referenced from:

References and Notes
  1. University of Pennsylvania, Philadelphia, Pennsylvania.
  2. Bergel, Morrison, and Rinderknecht (to Hoffmann-La Roche, Inc.), U. S. pat. 2,446,803 [C. A., 43, 695 (1949)].
  3. Horning and Finelli, J. Am. Chem. Soc., 71, 3204 (1949).
  4. Bruson and Riener, J. Am. Chem. Soc., 65, 25 (1943).

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

hydrochloric acid (7647-01-0)

methanol (67-56-1)

ether (60-29-7)

potassium hydroxide (1310-58-3)

magnesium sulfate (7487-88-9)

sodium amide (7782-92-5)

acrylonitrile (107-13-1)

β-chloropropionitrile (542-76-7)

tert-butyl alcohol (75-65-0)

Ethyl phenylcyanoacetate,
ethyl α-cyanophenylacetate (4553-07-5)

α-Phenyl-α-carbethoxyglutaronitrile,
Butyric acid, 2,4-dicyano-2-phenyl-, ethyl ester (53555-70-7)