A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1964, 44, 59
DOI: 10.15227/orgsyn.044.0059
[Succinic acid, α-ethyl-α-methyl-]
Submitted by F. S. Prout, V. N. Aguilar, F. H. Girard, D. D. Lee, and J. P. Shoffner1.
Checked by William G. Dauben and Dale L. Whalen.
1. Procedure
Potassium cyanide (71.6 g., 1.1 moles, U.S.P.) and 100 ml. of 95% ethanol are placed in a 2-l. round-bottomed flask having a ground joint and arranged with a Hershberg stirrer2 (Note 1). A solution of 113 g. (106 ml., 1 mole) of ethyl cyanoacetate, 79 g. (98 ml., 1.1 moles) of 2-butanone, and 66 ml. of glacial acetic acid is added to the stirred solution over a period of 1 hour. The mixture is stirred for an additional hour, the stirrer is removed, and the mixture is allowed to stand at room temperature for 7 days (Note 2).
Concentrated hydrochloric acid (500 ml.) is added to the semisolid reaction mixture, a reflux condenser is placed on the flask, and the mixture is heated under vigorous reflux for a period of 4 hours (Note 3). An additional 500 ml. of hydrochloric acid is added, and the boiling under reflux is continued for an additional 4 hours.
The cooled reaction mixture is extracted (Note 4) with four portions of ether (400 ml., 250 ml., 200 ml., 200 ml.) (Note 5) The ether extracts are filtered and combined, and about two-thirds of the ether is distilled. The ethereal solution is transferred to a 500-ml. Erlenmeyer flask, and the remaining ether is removed. The residue (about 160 g.) is dissolved in 200 ml. of 24% hydrochloric acid (1 part water, 2 parts concentrated hydrochloric acid) and the solution distilled until the boiling point reaches 108° (Note 6) The solution is cooled and allowed to stand at 5° for about 20 hours. The product is collected by vacuum filtration and dried in a vacuum desiccator containing both concentrated sulfuric acid and potassium hydroxide pellets. The yield of α-ethyl-α-methylsuccinic acid is 65–75 g. (41–47%), m.p. 91–97°. Concentration of the mother liquor to 125 ml. gives an additional 8–9 g. of acid, m.p. 85–91° (Note 7).
2. Notes
1. The reaction can be run in an open flask because only a small amount of gas escapes. See (Note 3). Sodium cyanide can be substituted for potassium cyanide if 2 g. of β-alanine is also employed as a catalyst.
2. Heating the reaction for shorter periods gave erratic results. At this point the semisolid mixture can be diluted with 200 ml. of water, extracted with benzene, and the benzene extract fractionally distilled to give ethyl 2,3-dicyano-3-methylpentanoate, b.p. 146.0–147.5° (2.5 mm.), n27D 1.4429 (highly purified ester has b.p. 138.5–141.5° (2 mm.), n25D 1.4432). The overall yield of α-ethyl-α-methylsuccinic acid is decreased by about 5% when the dicyano intermediate is isolated.
3. During the reflux period, gases are continuously evolved; these apparently are hydrogen chloride, carbon dioxide, ethyl acetate, and possibly ethyl chloride. The reaction should be run in a hood, or the gases should be trapped.3
4. If no layer separates on addition of the ether, add 200 ml. of water.
5. This extraction, designed to remove organic acids from inorganic salts, may also be effected with a lighter-than-water Kutscher-Steudel extractor.4
6. The distillate consists of low-boiling solvents.
7. The acid can be purified further by dissolving 50 g. of it in 100 ml. of benzene. The solution is filtered, diluted with 100 ml. of hexane, and cooled to 5°. The yield of acid is 45.0 g., m.p. 97–102° (lit.5 m.p. 101–102°).
3. Discussion
The one-step condensation to convert 2-butanone, ethyl cyanoacetate, and hydrocyanic acid to ethyl 2,3-dicyano-3-methylpentanoate is a modification of the procedure described by Smith and Horowitz5 in which pyridine acetate was employed as the catalyst. Higson and Thorp6 employed a two-step procedure in which butanone was converted to its cyanohydrin, which in turn was condensed with ethyl cyanoacetate.
α-Ethyl-α-methylsuccinic acid also has been prepared by the sulfuric acid hydrolysis of ethyl α-ethyl-α-methyl-β-carbethoxysuccinate,7 the action of 80% sulfuric acid on 1-ethoxy-3-ethyl-3-methyl-1,2-cyclopropanedioic acid,8 and the dichromate oxidation of β-ethyl-β-methylbutyrolactone.9
4. Merits of the Preparation
This procedure illustrates a process which should be general for many α,α-disubstituted succinic acids. It is more convenient than those previously employed because the reaction sequence is carried out in one step.

References and Notes
  1. Department of Chemistry, DePaul University, Chicago, Illinois.
  2. Org. Syntheses, Coll. Vol. 2, 116 (1943).
  3. Org. Syntheses, Coll. Vol. 2, 4 (1943); J. Cason and H. Rapoport, "Laboratory Text in Organic Chemistry," 3rd. Ed., Prentice-Hall, Inc., Engle-wood Cliffs, N.J. (1970), p. 95.
  4. L. C. Craig and D. Craig, in A. Weissberger, "Technique of Organic Chemistry," Vol. III, Part I, 2nd Ed., Interscience Publishers, New York (1956), p. 230. Org. Syntheses, Coll. Vol. 3, 539 (1955).
  5. P. A. S. Smith and J. P. Horowitz, J. Am. Chem. Soc., 71, 3418 (1949).
  6. A. Higson and J. F. Thorpe, J. Chem. Soc., 89, 1467 (1906).
  7. K. Auwers and R. Fritzweiler, Ann., 298, 166 (1897).
  8. B. Singh and J. F. Thorpe, J. Chem. Soc., 123, 113 (1923).
  9. S. S. G. Guha-Sircar, J. Chem. Soc., 898 (1928).

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

ethanol (64-17-5)

sulfuric acid (7664-93-9)

hydrogen chloride,
hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

Benzene (71-43-2)

ethyl acetate (141-78-6)

ether (60-29-7)

sodium cyanide (143-33-9)

hydrocyanic acid (74-90-8)

potassium cyanide (151-50-8)

carbon dioxide (124-38-9)

potassium hydroxide (1310-58-3)

Ethyl cyanoacetate (105-56-6)

β-Alanine (107-95-9)

2-butanone (78-93-3)

hexane (110-54-3)

ethyl chloride (75-00-3)

α-Ethyl-α-methylsuccinic acid,
Succinic acid, α-ethyl-α-methyl- (631-31-2)

ethyl 2,3-dicyano-3-methylpentanoate

pyridine acetate

ethyl α-ethyl-α-methyl-β-carbethoxysuccinate

1-ethoxy-3-ethyl-3-methyl-1,2-cyclopropanedioic acid